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Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk | Anticancer Research
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//cdn.jsdelivr.net" /> <link rel="dns-prefetch" href="//cdn.foxycart.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <link rel="canonical" href="https://ar.iiarjournals.org/content/45/2/465" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/45/2/465.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/45/2/465.full.txt" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/45/2/465.ppt" /> <meta name="issue_cover_image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/45/2.cover-source.jpg" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/anticanres/45/2/465.atom" /> <meta name="HW.pisa" content="anticanres;45/2/465" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk" /> <meta name="DC.Identifier" content="10.21873/anticanres.17436" /> <meta name="DC.Date" content="2025-02-01" /> <meta name="DC.Publisher" content="International Institute of Anticancer Research" /> <meta name="DC.Rights" content="Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0)." /> <meta name="DC.AccessRights" content="open-access" /> <meta name="DC.Description" content="Background/Aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. Patients and Methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms." /> <meta name="DC.Contributor" content="PO-CHUEN SHIEH" /> <meta name="DC.Contributor" content="HOU-YU SHIH" /> <meta name="DC.Contributor" content="CHIN-LIANG CHUANG" /> <meta name="DC.Contributor" content="CHIA-WEN TSAI" /> <meta name="DC.Contributor" content="WEN-SHIN CHANG" /> <meta name="DC.Contributor" content="MENG-GI BAU" /> <meta name="DC.Contributor" content="YUN-CHI WANG" /> <meta name="DC.Contributor" content="TE-CHUN HSIA" /> <meta name="DC.Contributor" content="DA-TIAN BAU" /> <meta name="DC.Contributor" content="JAI-SING YANG" /> <meta name="article:published_time" content="2025-02-01" /> <meta name="article:section" content="Experimental Studies" /> <meta name="citation_title" content="Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk" /> <meta name="citation_abstract" lang="en" content="<p>Background/Aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. Patients and Methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms.</p>" /> <meta name="citation_journal_title" content="Anticancer Research" /> <meta name="citation_publisher" content="International Institute of Anticancer Research" /> <meta name="citation_publication_date" content="2025/02/01" /> <meta name="citation_mjid" content="anticanres;45/2/465" /> <meta name="citation_id" content="45/2/465" /> <meta name="citation_public_url" content="https://ar.iiarjournals.org/content/45/2/465" /> <meta name="citation_abstract_html_url" content="https://ar.iiarjournals.org/content/45/2/465.abstract" /> <meta name="citation_full_html_url" content="https://ar.iiarjournals.org/content/45/2/465.full" /> <meta name="citation_pdf_url" content="https://ar.iiarjournals.org/content/anticanres/45/2/465.full.pdf" /> <meta name="citation_issn" content="0250-7005" /> <meta name="citation_issn" content="1791-7530" /> <meta name="citation_doi" content="10.21873/anticanres.17436" /> <meta name="citation_pmid" content="39890168" /> <meta name="citation_volume" content="45" /> <meta name="citation_issue" content="2" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Experimental Studies" /> <meta name="citation_firstpage" content="465" /> <meta name="citation_lastpage" content="471" /> <meta name="citation_access" content="all" /> <meta name="citation_author" content="PO-CHUEN SHIEH" /> <meta name="citation_author_institution" content="Department of Pharmacy, Tajen University, Pingtung, Taiwan, R.O.C." /> <meta name="citation_author" content="HOU-YU SHIH" /> <meta name="citation_author_institution" content="Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C." /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author" content="CHIN-LIANG CHUANG" /> <meta name="citation_author_institution" content="Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author_institution" content="National Defense Medical Center, Taipei, Taiwan, R.O.C." /> <meta name="citation_author" content="CHIA-WEN TSAI" /> <meta name="citation_author_institution" content="Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C." /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author" content="WEN-SHIN CHANG" /> <meta name="citation_author_institution" content="Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C." /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author" content="MENG-GI BAU" /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author" content="YUN-CHI WANG" /> <meta name="citation_author_institution" content="Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C." /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C." /> <meta name="citation_author" content="TE-CHUN HSIA" /> <meta name="citation_author_institution" content="Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical 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Zheng;citation_title=Associations between various possible promoter polymorphisms of MMPs genes and endometriosis risk: a meta-analysis;citation_pages=174-188;citation_volume=205;citation_year=2016;citation_pmid=27620811;citation_doi=10.1016/j.ejogrb.2016.08.015" /> <meta name="citation_reference" content="citation_journal_title=Revista da Associação Médica Brasileira;citation_journal_abbrev=Rev Assoc Med Bras;citation_author=AB. Trovó de Marqui;citation_title=Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling.;citation_pages=620-632;citation_volume=58;citation_year=2012;citation_issue=5;citation_pmid=23090236;citation_doi=10.1590/s0104-42302012000500022" /> <meta name="citation_fulltext_world_readable" content="" /> <meta name="twitter:title" content="Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/45/2.cover-source.jpg" /> <meta name="twitter:description" content="Background/Aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. Patients and Methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms." /> <meta name="og-title" property="og:title" content="Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk" /> <meta name="og-url" property="og:url" content="https://ar.iiarjournals.org/content/45/2/465" /> <meta name="og-site-name" property="og:site_name" content="Anticancer Research" /> <meta name="og-description" property="og:description" content="Background/Aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. Patients and Methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/45/2.cover-source.jpg" /> <link rel="shortlink" href="/node/83138" /> <link rel="shortcut icon" href="https://ar.iiarjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <title>Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk | Anticancer Research</title> <link type="text/css" rel="stylesheet" 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class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a"> <div class="highwire-cite-overline"><span class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Experimental Studies</span></span></div> <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access hw-icon-open-access" title="Open Access" aria-hidden="true"></i><span class="element-invisible highwire-access-icon highwire-access-icon-open-access" style="">Open Access</span></span></div> <h1 class="highwire-cite-title" id="page-title">Association of <em>Matrix Metalloproteinase-1</em> Promoter Genotypes With Endometriosis Risk</h1> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">PO-CHUEN SHIEH</span>, <span class="highwire-citation-author" data-delta="1">HOU-YU SHIH</span>, <span class="highwire-citation-author" data-delta="2">CHIN-LIANG CHUANG</span>, <span class="highwire-citation-author" data-delta="3">CHIA-WEN TSAI</span>, <span class="highwire-citation-author" data-delta="4">WEN-SHIN CHANG</span>, <span class="highwire-citation-author" data-delta="5">MENG-GI BAU</span>, <span class="highwire-citation-author" data-delta="6">YUN-CHI WANG</span>, <span class="highwire-citation-author" data-delta="7">TE-CHUN HSIA</span>, <span class="highwire-citation-author" data-delta="8">DA-TIAN BAU</span> and <span class="highwire-citation-author" data-delta="9">JAI-SING YANG</span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">February 2025, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">465-471; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.21873/anticanres.17436 </span></div> <div class="highwire-cite-extras"><span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Add to Cart (%short-price)" data-apath="/anticanres/45/2/465.atom" data-type="link" data-font-icon="" data-parent-id="83103"></span></div> </div> <div id="hw-article-author-popups-top-node-83138--6564889818" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">PO-CHUEN SHIEH </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pharmacy, Tajen University, Pingtung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=PO-CHUEN%2BSHIEH%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=SHIEH%20P&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3APO-CHUEN%2BSHIEH%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">HOU-YU SHIH </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HOU-YU%2BSHIH%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=SHIH%20H&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHOU-YU%2BSHIH%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">CHIN-LIANG CHUANG </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>4</span>Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>5</span>National Defense Medical Center, Taipei, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=CHIN-LIANG%2BCHUANG%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=CHUANG%20C&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ACHIN-LIANG%2BCHUANG%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">CHIA-WEN TSAI </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=CHIA-WEN%2BTSAI%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=TSAI%20C&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ACHIA-WEN%2BTSAI%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">WEN-SHIN CHANG </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=WEN-SHIN%2BCHANG%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=CHANG%20W&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AWEN-SHIN%2BCHANG%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">MENG-GI BAU </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=MENG-GI%2BBAU%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=BAU%20M&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AMENG-GI%2BBAU%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">YUN-CHI WANG </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=YUN-CHI%2BWANG%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=WANG%20Y&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AYUN-CHI%2BWANG%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">TE-CHUN HSIA </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=TE-CHUN%2BHSIA%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=HSIA%20T&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ATE-CHUN%2BHSIA%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">DA-TIAN BAU </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>7</span>Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=DA-TIAN%2BBAU%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=BAU%20D&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ADA-TIAN%2BBAU%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:artbau2@gmail.com" class="" data-icon-position="" data-hide-link-title="0">artbau2@gmail.com</a></span></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">JAI-SING YANG </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span>Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.</div><div class='author-affiliation'><span class='nlm-sup'>8</span>Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=JAI-SING%2BYANG%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=YANG%20J&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJAI-SING%2BYANG%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:jaisingyang@gmail.com" class="" data-icon-position="" data-hide-link-title="0">jaisingyang@gmail.com</a></span></li></ul></div></div></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> <div class="panel-row-wrapper clearfix"> <div class="main-content-wrapper grid-17 suffix-1 alpha"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs" > <div class="pane-content"> <div class="item-list"><ul class="tabs inline panels-ajax-tab"><li class="first"><a href="/content/45/2/465" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_art" data-target-id="highwire_article_tabs" data-entity-context="node:83138" data-trigger="" data-url-enabled="1">Article</a><a href="/panels_ajax_tab/jnl_iiar_tab_art/node:83138/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/2/465/tab-figures-data" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_data" data-target-id="highwire_article_tabs" data-entity-context="node:83138" data-trigger="tab-figures-data" data-url-enabled="1">Figures & Data</a><a href="/panels_ajax_tab/jnl_iiar_tab_data/node:83138/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/2/465/tab-article-info" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_info" data-target-id="highwire_article_tabs" data-entity-context="node:83138" 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src="https://ar.iiarjournals.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-jnl_iiar_tab_art"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-markup" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article fulltext-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><p id="p-5">Background/Aim: Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. Patients and Methods: This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). Conclusion: The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms.</p></div><span class="kwd-group-title">Key Words:</span><ul class="kwd-group"><li class="kwd"><a href="/keyword/endometriosis" class="hw-term hw-article-keyword hw-article-keyword-endometriosis" rel="nofollow">Endometriosis</a></li><li class="kwd"><a href="/keyword/metalloproteinase-1" class="hw-term hw-article-keyword hw-article-keyword-metalloproteinase-1" rel="nofollow">metalloproteinase-1</a></li><li class="kwd"><a href="/keyword/polymorphism" class="hw-term hw-article-keyword hw-article-keyword-polymorphism" rel="nofollow">polymorphism</a></li><li class="kwd"><a href="/keyword/taiwan" class="hw-term hw-article-keyword hw-article-keyword-taiwan" rel="nofollow">Taiwan</a></li></ul><p id="p-6">Endometriosis is a chronic, hormone-dependent, and inflammatory gynecological condition, affecting up to 10% of women of reproductive age (<a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a>, <a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a>). It is a complex disorder characterized by the growth of endometrial-like tissue outside the uterus, which can cause chronic pelvic pain and infertility (<a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3</a>, <a id="xref-ref-4-1" class="xref-bibr" href="#ref-4">4</a>). In Taiwan, the reported prevalence of endometriosis has shown an upward trend, ranging from 1.5% to 30.8% among women of childbearing age (<a id="xref-ref-5-1" class="xref-bibr" href="#ref-5">5</a>-<a id="xref-ref-7-1" class="xref-bibr" href="#ref-7">7</a>). Moreover, women diagnosed with endometriosis exhibit an increased risk of developing several malignancies, including ovarian, endometrial, cervical, breast and colorectal cancers (<a id="xref-ref-8-1" class="xref-bibr" href="#ref-8">8</a>-<a id="xref-ref-13-1" class="xref-bibr" href="#ref-13">13</a>). The hypothesis of hereditary factors playing an important role is strongly supported by Bellelis and his colleagues, reporting that approximately 5.3% of the cases have first-degree family history (<a id="xref-ref-14-1" class="xref-bibr" href="#ref-14">14</a>). One important issue to consider is that endometriosis is a female disease characterized by notable heterogeneity and an unclear pathogenesis (<a id="xref-ref-15-1" class="xref-bibr" href="#ref-15">15</a>, <a id="xref-ref-16-1" class="xref-bibr" href="#ref-16">16</a>). Thus, one of the major challenges is the lack of reliable predictive biomarkers (<a id="xref-ref-17-1" class="xref-bibr" href="#ref-17">17</a>, <a id="xref-ref-18-1" class="xref-bibr" href="#ref-18">18</a>).</p><p id="p-7">Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a critical role in the degradation of extracellular matrix (ECM) components (<a id="xref-ref-19-1" class="xref-bibr" href="#ref-19">19</a>). Beyond ECM turnover, MMPs regulate fundamental cellular processes such as proliferation, differentiation, migration, and apoptosis, many of which are intricately linked to carcinogenic mechanisms (<a id="xref-ref-20-1" class="xref-bibr" href="#ref-20">20</a>). In the 1990s, MMPs were first identified as key mediators in uterine tissue remodeling during menstrual cycles and embryo implantation. Dysregulation of MMP activity was subsequently hypothesized to contribute to the pathogenesis of endometriosis (<a id="xref-ref-21-1" class="xref-bibr" href="#ref-21">21</a>-<a id="xref-ref-23-1" class="xref-bibr" href="#ref-23">23</a>). Over the past decades, heightened expression of matrix metalloproteinases (MMPs) has been consistently detected in ectopic tissues of individuals with endometriosis. This aberrant expression indicates a critical role for specific MMPs, such as MMP-2 (<a id="xref-ref-24-1" class="xref-bibr" href="#ref-24">24</a>, <a id="xref-ref-25-1" class="xref-bibr" href="#ref-25">25</a>), MMP-3 (<a id="xref-ref-26-1" class="xref-bibr" href="#ref-26">26</a>), and MMP-9 (<a id="xref-ref-25-2" class="xref-bibr" href="#ref-25">25</a>, <a id="xref-ref-27-1" class="xref-bibr" href="#ref-27">27</a>), in the pathogenesis and progression of the condition. Above all, MMP-1 has been highlighted for its significant involvement in endometriosis. Its expression correlates with the activity of endometriotic lesions, implicating it as a key factor in the pathophysiology of the condition (<a id="xref-ref-28-1" class="xref-bibr" href="#ref-28">28</a>, <a id="xref-ref-29-1" class="xref-bibr" href="#ref-29">29</a>).</p><p id="p-8">The <em>MMP-1</em> gene, located on chromosome 11q22.3, encodes the MMP-1 enzyme (<a id="xref-ref-30-1" class="xref-bibr" href="#ref-30">30</a>, <a id="xref-ref-31-1" class="xref-bibr" href="#ref-31">31</a>) (<a id="xref-fig-1-1" class="xref-fig" href="#F1">Figure 1</a>). Among its genetic variants, the rs1799750 polymorphism (rs796666299, rs375359915, rs368625565, rs139258005, rs17886084, and rs11292517 have been merged into the same polymorphism), situated 1607 base pairs upstream of the promoter region, has been the most intensively studied. This polymorphism has been found to be associated with specific types of cancer (<a id="xref-ref-32-1" class="xref-bibr" href="#ref-32">32</a>, <a id="xref-ref-33-1" class="xref-bibr" href="#ref-33">33</a>), but not with others (<a id="xref-ref-34-1" class="xref-bibr" href="#ref-34">34</a>, <a id="xref-ref-35-1" class="xref-bibr" href="#ref-35">35</a>). Numerous studies have explored the potential role of the <em>MMP-1</em> rs1799750 polymorphism in predisposing individuals to endometriosis across different populations (<a id="xref-ref-36-1" class="xref-bibr" href="#ref-36">36</a>-<a id="xref-ref-39-1" class="xref-bibr" href="#ref-39">39</a>). Given these findings, we aimed to investigate the association between <em>MMP-1</em> rs1799750 genotypes and the risk of endometriosis in a Taiwanese cohort comprising 203 patients with endometriosis and 636 non-endometriosis controls. This study examined the influence of <em>MMP-1</em> polymorphisms on the susceptibility to endometriosis, thereby enhancing our understanding of the complex molecular mechanisms underlying the disease. Additionally, these findings may pave the way for novel approaches in the prevention and treatment of endometriosis.</p><div id="F1" class="fig pos-float odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="https://ar.iiarjournals.org/content/anticanres/45/2/465/F1.large.jpg?width=800&height=600&carousel=1" title="Physical map of MMP-1 rs1799750 polymorphic site in human chromosome 11." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1267016074" data-figure-caption="<div class="highwire-markup">Physical map of MMP-1 rs1799750 polymorphic site in human chromosome 11.</div>" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Figure 1." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="https://ar.iiarjournals.org/content/anticanres/45/2/465/F1.medium.gif" width="440" height="263"/><noscript><img class="highwire-fragment fragment-image" alt="Figure 1." src="https://ar.iiarjournals.org/content/anticanres/45/2/465/F1.medium.gif" width="440" height="263"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="https://ar.iiarjournals.org/content/anticanres/45/2/465/F1.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Figure 1." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="https://ar.iiarjournals.org/content/anticanres/45/2/465/F1.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/83207" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption" xmlns:xhtml="http://www.w3.org/1999/xhtml"><span class="fig-label">Figure 1.</span> <p id="p-9" class="first-child">Physical map of MMP-1 rs1799750 polymorphic site in human chromosome 11.</p><div class="sb-div caption-clear"></div></div></div><div class="section patients-methods" id="sec-1"><h2 class="">Patients and Methods</h2><p id="p-10"><em>Selection of endometriosis females and non-endometriosis controls</em>. This study included a total of 203 women diagnosed with endometriosis and a matched cohort of 636 women without endometriosis as controls. Age-matching criteria were applied, with controls selected to be within ±5 years of the corresponding cases. All patients with endometriosis were recruited from China Medical University Hospital, located in central Taiwan.</p><p id="p-11">Participants were excluded from the control group if they had any history of leiomyoma, adenomyosis, or malignancies involving the uterus, cervix, or ovaries. Additionally, women who had undergone hormone therapy within the past 12 months were also excluded. To further reduce the possibility of misclassifying individuals with undiagnosed endometriosis as controls, a comprehensive screening process was implemented. Control candidates reporting symptoms such as pelvic pain or exhibiting signs suggestive of endometriosis during the questionnaire interview were referred for pelvic examinations, ultrasonography, or magnetic resonance imaging (MRI). Those with any findings indicative of endometriosis were subsequently excluded from the control group.</p><p id="p-12"><em>Genotyping methodology for MMP-1 promoter polymorphisms</em>. Peripheral blood samples were carefully obtained from all participants, with genomic DNA extracted within 24 h of collection following standard procedures (<a id="xref-ref-40-1" class="xref-bibr" href="#ref-40">40</a>, <a id="xref-ref-41-1" class="xref-bibr" href="#ref-41">41</a>). Genotyping of the <em>MMP-1</em> rs1799750 polymorphism was performed using a protocol previously described in detail (<a id="xref-ref-42-1" class="xref-bibr" href="#ref-42">42</a>). The polymerase chain reaction (PCR) conditions for <em>MMP-1</em> rs1799750 analysis included an initial denaturation step at 94°C for 5 min, followed by 35 cycles consisting of denaturation at 94°C for 30 s, annealing at 57°C for 30 s, and extension at 72°C for 30 s. A final extension step was conducted at 72°C for 10 min, after which the reaction was cooled and sustained to 25°C.</p><p id="p-13"><em>Statistical methodology</em>. The adherence of the control group’s genotype frequencies to Hardy-Weinberg equilibrium (HWE) was evaluated using the goodness-of-fit Chi-square test. Differences in age distribution between cases and controls were analyzed with the Student’s <em>t</em>-test. Variations in the distribution of <em>MMP-1</em> genotypes between endometriosis and non- endometriosis groups were assessed using the Pearson’s Chi-square test. To determine the association between <em>MMP-1</em> genotypes and the risk of endometriosis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Statistical significance was defined as any <em>p</em>-value less than 0.05.</p></div><div class="section results" id="sec-2"><h2 class="">Results</h2><p id="p-14"><em>Demographic and lifestyle characteristics of study participants</em>. <a id="xref-table-wrap-1-1" class="xref-table" href="#T1">Table I</a> summarizes the demographic and lifestyle characteristics, including age, age at menarche, full-term pregnancy status, smoking habits, and alcohol consumption, for the 203 women diagnosed with endometriosis and the 636 non-endometriosis controls. Through careful age-matching, no significant differences were observed between the two groups in terms of age distribution (<em>p</em>=0.3732) or age at menarche (<em>p</em>=0.3378). A significantly lower proportion of endometriosis patients (63.1%) reported having experienced a full-term pregnancy compared to the control group (<em>p</em>=0.0005). In contrast, the prevalence of smoking and alcohol consumption did not differ significantly between the groups (<em>p</em>=0.6470 and <em>p</em>=0.9387, respectively). Among the endometriosis cases, 21.2% were classified as early stage (Stage I or II), while the remaining 78.8% were categorized as advanced stage (Stage III or IV), as shown in <a id="xref-table-wrap-1-2" class="xref-table" href="#T1">Table I</a>.</p><div id="T1" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/83199/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/83199/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/83199" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table I.</span> <p id="p-15" class="first-child">Demographics of the 203 females with endometriosis and 636 non-endometriosis controls.</p><div class="sb-div caption-clear"></div></div></div><p id="p-16"><em>Association of MMP-1 rs1799750 genotypes with endometriosis susceptibility</em>. The distribution of <em>MMP-1</em> rs1799750 genotypes among the 203 endometriosis cases and 636 non-endometriosis controls is comprehensively outlined in <a id="xref-table-wrap-2-1" class="xref-table" href="#T2">Table II</a>. First, the genotype frequencies within the control group were consistent with Hardy-Weinberg equilibrium (<em>p</em>=0.0870). Second, a comparative analysis revealed statistically significant differences in the overall distribution of <em>MMP-1</em> rs1799750 genotypes between endometriosis cases and controls (<em>p</em> for trend=0.0092, <a id="xref-table-wrap-2-2" class="xref-table" href="#T2">Table II</a>). Further evaluation indicated that the 2G/1G and 1G/1G genotypes were significantly less prevalent among endometriosis patients compared to controls, suggesting protective effects (OR=0.67, 95%CI=0.48-0.94, <em>p</em>=0.0226; and OR=0.45, 95%CI=0.23-0.86, <em>p</em>=0.0204, respectively; <a id="xref-table-wrap-2-3" class="xref-table" href="#T2">Table II</a>). Additionally, when considering the combined genotypes 2G/2G+2G/1G compared to 1G/1G, a borderline statistical significance was observed (OR=0.54, 95%CI=0.29-1.03, <em>p</em>=0.0769). The association became more pronounced when contrasting 2G/2G with the pooled genotypes 2G/1G+1G/1G (OR=0.63, 95%CI=0.46-0.87, <em>p</em>=0.0058). Taken together, these findings indicate that individuals carrying the 1G/1G genotype exhibit a reduced risk of developing endometriosis in the Taiwanese population (<a id="xref-table-wrap-2-4" class="xref-table" href="#T2">Table II</a>).</p><div id="T2" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/83226/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/83226/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/83226" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table II.</span> <p id="p-17" class="first-child">Distributions of MMP-1 rs1799750 genotypes in females with endometriosis and non-endometriosis controls.</p><div class="sb-div caption-clear"></div></div></div><p id="p-18"><em>Validation of the MMP-1 rs1799750 1G allele as protective against endometriosis</em>. <a id="xref-table-wrap-3-1" class="xref-table" href="#T3">Table III</a> details the allelic distribution of the <em>MMP-1</em> rs1799750 polymorphism among endometriosis patients and non-endometriosis controls. Consistent with the genotype analysis presented in <a id="xref-table-wrap-2-5" class="xref-table" href="#T2">Table II</a>, individuals carrying the 1G allele at the <em>MMP-1</em> rs1799750 locus demonstrated a significantly reduced risk of developing endometriosis compared to those with the 2G allele (OR=0.69, 95%CI=0.54-0.88, <em>p</em>=0.0037, <a id="xref-table-wrap-3-2" class="xref-table" href="#T3">Table III</a>). This result reinforces the protective role of the 1G allele in reducing susceptibility to endometriosis.</p><div id="T3" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/83298/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/83298/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/83298" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table III.</span> <p id="p-19" class="first-child">Distribution of MMP-1 rs1799750 allelic frequencies in females with endometriosis and non-endometriosis controls.</p><div class="sb-div caption-clear"></div></div></div></div><div class="section discussion" id="sec-3"><h2 class="">Discussion</h2><p id="p-20">MMP-1 is a critical enzyme involved in the breakdown and remodeling of the extracellular matrix, processes closely linked to cellular migration and invasion (<a id="xref-ref-43-1" class="xref-bibr" href="#ref-43">43</a>, <a id="xref-ref-44-1" class="xref-bibr" href="#ref-44">44</a>). The inhibition of MMP activity, including MMP-1, through the administration of MMP inhibitor III in a chicken chorioallantoic membrane model significantly suppressed the formation of endometriosis-like lesions. This finding underscores the potential contribution of MMP-1, along with MMP-2, -3, -7, and -13, to the development of endometriotic lesions (<a id="xref-ref-45-1" class="xref-bibr" href="#ref-45">45</a>). Despite these insights, it remains unclear whether variations in MMP-1 expression are predominantly governed by genetic factors and whether the <em>MMP-1</em> rs1799750 polymorphism could serve as a reliable predictive biomarker for endometriosis.</p><p id="p-21">Thus, in the present study, the potential impact of <em>MMP-1</em> rs1799750 polymorphism on endometriosis susceptibility was meticulously examined in a Taiwan cohort, encompassing a cohort of 203 individuals with endometriosis and 636 age-matched non-endometriosis controls (<a id="xref-table-wrap-1-3" class="xref-table" href="#T1">Table I</a>). The <em>MMP-1</em> rs1799750 polymorphism has been hypothesized to generate an E-twenty six-binding site, potentially enhancing transcriptional activity (<a id="xref-ref-46-1" class="xref-bibr" href="#ref-46">46</a>). Previous investigations into the association between the <em>MMP-1</em> rs1799750 polymorphism and endometriosis risk have yielded conflicting outcomes. First in 2005, Shan and his colleagues examined this polymorphism in a China cohort and reported that the 2G allele was significantly more prevalent among patients with endometriosis compared to controls. Additionally, they pointed out that the 2G/1G and 2G/2G genotypes were linked to an elevated risk of endometriosis (<a id="xref-ref-37-1" class="xref-bibr" href="#ref-37">37</a>). Similar findings were corroborated by Mao and his colleagues with a relatively smaller sample size (<a id="xref-ref-47-1" class="xref-bibr" href="#ref-47">47</a>).</p><p id="p-22">Conversely, Ferrari and his colleagues found no significant differences in allele or genotype frequencies between endometriosis patients and controls within an Italian cohort (<a id="xref-ref-38-1" class="xref-bibr" href="#ref-38">38</a>). Two years later, Borghese and his colleagues examined the contribution of <em>MMP-1</em> rs1799750 genotypes to endometriosis among a French cohort, brought another piece of negative association evidence (<a id="xref-ref-39-2" class="xref-bibr" href="#ref-39">39</a>). The discrepancies between Shan’s results with Ferrari’s and Borghese’s findings may stem from several potential factors, including larger sample sizes in Shan’s study (<a id="xref-ref-37-2" class="xref-bibr" href="#ref-37">37</a>), a higher proportion of late-stage (III and IV) endometriosis cases, ethnic differences in the investigated populations (Asian <em>versus</em> Caucasian), and the genotyping methodology employed (PCR-RFLP). The work of Borghese even does not provide genotyping details, instead, they only presented the non-significant statistical outcomes (<a id="xref-ref-39-3" class="xref-bibr" href="#ref-39">39</a>). Despite these observations, the limitations of our study, such as sample size and the number of comparable studies, warrant cautious interpretation of the findings. All epidemiological studies examining the association between <em>MMP-1</em> rs1799750 genotypes and endometriosis risk are summarized in <a id="xref-table-wrap-4-1" class="xref-table" href="#T4">Table IV</a>, along with a concise summary of their highlight findings. Future studies with larger cohorts and more diverse populations are needed to confirm these results and clarify the role of the <em>MMP-1</em> rs1799750 polymorphism in endometriosis susceptibility. The limited sample size also restricted us from further evaluating of <em>MMP-1</em> rs1799750 genotypes to different (early and late) stages of endometriosis, which currently showed no preference (data not shown).</p><div id="T4" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/83184/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/83184/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/83184" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table IV.</span> <p id="p-23" class="first-child">Summary of previous and current studies focusing on the association of MMP-1 rs1799750 with endometriosis.</p><div class="sb-div caption-clear"></div></div></div><p id="p-24">This study represents the most extensive epidemiological investigation to date on the role of <em>MMP-1</em> in the etiology of endometriosis, with a significantly larger scale compared to previous studies (control:case ratio of 636:203 in the present study <em>versus</em> smaller cohorts in prior reports) (<a id="xref-table-wrap-4-2" class="xref-table" href="#T4">Table IV</a>). While the small sample sizes of earlier studies may have weakened the strength of their evidence, findings from Asian countries, consistently suggest that the 1G allele of <em>MMP-1</em> rs1799750 functions as a protective genetic marker similar to our findings (<a id="xref-table-wrap-2-6" class="xref-table" href="#T2">Table II</a> and <a id="xref-table-wrap-3-3" class="xref-table" href="#T3">Table III</a>). In contrast, studies involving Western populations have generally indicated that the genotypes of <em>MMP-1</em> rs1799750 lack the capacity as a practical biomarker for endometriosis prediction (<a id="xref-table-wrap-4-3" class="xref-table" href="#T4">Table IV</a>). This dichotomy aligns with hypotheses proposed in meta-analysis review articles published in 2015 and 2016 (<a id="xref-ref-48-1" class="xref-bibr" href="#ref-48">48</a>, <a id="xref-ref-49-1" class="xref-bibr" href="#ref-49">49</a>), highlighting the need for further research to draw definitive conclusions. Additionally, we examined the association of <em>MMP-1</em> rs1799750 genotypes with various demographic and lifestyle factors, including age, age at menarche, full-term pregnancy status, smoking, and alcohol consumption. However, stratified analyses revealed no significant intergroup differences in these subcategories (data not shown).</p><p id="p-25">In conclusion, our findings suggest that the <em>MMP-1</em> rs1799750 1G/1G genotype is associated with a reduced risk of endometriosis, and individuals possessing the 1G allele may experience a lower susceptibility to the condition. To establish its utility as a predictive biomarker, further validation of the <em>MMP-1</em> rs1799750 variant is warranted across diverse populations, especially Asian populations. The findings may provide significant benefits in mitigating the prevalence of endometriosis in Taiwan.</p></div><div class="section ack" id="ack-1"><h2 class="">Acknowledgements</h2><p id="p-28">The Authors are grateful to Yu-Hsin Yen and Yu-Cheng Luo for their excellent technical assistance. All the participants in this study are also appreciated. This study was supported by Taichung Armed Forces General Hospital (grant number: TCAFGH_D_114015), and China Medical University and Hospital (grand number: DMR-114-098).</p></div><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn" id="fn-2"><p id="p-2"><strong>Authors’ Contributions</strong></p><p id="p-3">Research design: Shieh PC, Yang JS, Bau DT; Summary of questionnaires: Shih HY, Chuang CL, Hsia TC; Experiment performance: Shih HY, Yang JS, Tsai CW, Chang WS; Statistical analysis and confirmation: Shih HY, Wang YC, Tsai CW, Bau MG, Hsia TC; Manuscript writing: Shieh PC, Chuang CL, Yang JS, Bau DT; Polishing and correction: Yang JS, Bau DT.</p></li><li class="fn" id="fn-3"><p id="p-26"><strong>Conflicts of Interest</strong></p><p id="p-27">The Authors have no conflicts of interest to declare in relation to this study.</p></li></ul></div><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2025-01-03"><span class="received-label">Received </span>January 3, 2025.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2025-01-14"><span class="rev-recd-label">Revision received </span>January 14, 2025.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2025-01-15"><span class="accepted-label">Accepted </span>January 15, 2025.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">Copyright © 2025 International Institute of Anticancer Research (Dr. George J. 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