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(PDF) Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome | Luis Caleb Mercado Alvarez - Academia.edu
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The two most common variants are migraine with (MA) and without (MO) aura. Often considered to be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately childhood condition characterized by severe, discrete episodes of nausea, vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease, and several other factors. Temporal temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and RFLP was used to screen almost 90% of the mtDNA, including the control region (CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVSþ) and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence variants were found in six CVSþ and in zero control subjects (P ¼ 0.003). These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 (HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the nt 16040-16188 segment of HV1 that includes the termination associated sequence (TAS), a functional location important in the regulation of mtDNA replication. Based upon our findings, sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVSþ, 30 randomlyascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases. Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold more common relative to control subjects in both CVS groups (P ¼ 0.01 combined data) and in MO (P ¼ 0.02), but not in MA (P ¼ 0.5 vs. control subjects and 0.02 vs. MO). No group differences were noted in the remainder of HV1. We conclude that sequence variation in this small ''peri-TAS'' segment is associated with CVS and MO, but not MA. These variants likely constitute risk factors for disease development. Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases, and the co-segregation in a maternal inheritance pattern of CVS and MO within families. A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implications, especially concerning the avoidance of fasting.","publication_date":"2004,,","publication_name":"American Journal of Medical Genetics","grobid_abstract_attachment_id":"53554929"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [53651164]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" 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translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="2530854" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/2530854/Are_pediatric_and_adult_onset_cyclic_vomiting_syndrome_CVS_biologically_different_conditions_Relationship_of_adult_onset_CVS_with_the_migraine_and_pediatric_CVS_associated_common_mtDNA_polymorphisms_16519T_and_3010A">Are pediatric and adult-onset cyclic vomiting syndrome (CVS) biologically different conditions? Relationship of adult-onset CVS with the migraine and pediatric CVS-associated common mtDNA polymorphisms 16519T and 3010A</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="3070540" href="https://usc.academia.edu/EssamZaki">Essam Zaki</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Are pediatric and adult-onset cyclic vomiting syndrome (CVS) biologically different conditions? Relationship of adult-onset CVS with the migraine and pediatric CVS-associated common mtDNA polymorphisms 16519T and 3010A","attachmentId":30546204,"attachmentType":"pdf","work_url":"https://www.academia.edu/2530854/Are_pediatric_and_adult_onset_cyclic_vomiting_syndrome_CVS_biologically_different_conditions_Relationship_of_adult_onset_CVS_with_the_migraine_and_pediatric_CVS_associated_common_mtDNA_polymorphisms_16519T_and_3010A","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/2530854/Are_pediatric_and_adult_onset_cyclic_vomiting_syndrome_CVS_biologically_different_conditions_Relationship_of_adult_onset_CVS_with_the_migraine_and_pediatric_CVS_associated_common_mtDNA_polymorphisms_16519T_and_3010A"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="100291731" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/100291731/Gene_centric_analysis_implicates_nuclear_encoded_mitochondrial_protein_gene_variants_in_migraine_susceptibility">Gene-centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32535419" href="https://afgsaa.academia.edu/LynGriffiths">Lyn Griffiths</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular genetics & genomic medicine, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">Migraine is a common neurological disorder which affects a large proportion of the population. The Norfolk Island population is a genetically isolated population and is an ideal discovery cohort for genetic variants involved in complex disease susceptibility given the reduced genetic and environmental heterogeneity. Given that the majority of proteins responsible for mitochondrial function are nuclear encoded, this study aimed to investigate the role of Nuclear Encoded Mitochondrial Protein (NEMP) genes in relation to migraine susceptibility. A gene-centric association analysis of NEMP genes was undertaken in the most related individuals (n = 315) within the genetically isolated Norfolk Island population. The discovery phase included genes with three or more SNP associations (P &lt; 0.005), which were investigated further in a replication phase using an unrelated migraine case-control cohort (544 patients and 584 controls). The discovery phase of the study implicated SNPs in 5 NEMP ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Gene-centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility","attachmentId":101155650,"attachmentType":"pdf","work_url":"https://www.academia.edu/100291731/Gene_centric_analysis_implicates_nuclear_encoded_mitochondrial_protein_gene_variants_in_migraine_susceptibility","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/100291731/Gene_centric_analysis_implicates_nuclear_encoded_mitochondrial_protein_gene_variants_in_migraine_susceptibility"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="77496492" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/77496492/Mitochondrial_genome_wide_association_study_of_migraine_the_HUNT_Study">Mitochondrial genome-wide association study of migraine – the HUNT Study</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="181452093" href="https://independent.academia.edu/Michaelkerry3">Michael kerry</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cephalalgia, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">Background Variation in mitochondrial DNA (mtDNA) has been indicated in migraine pathogenesis, but genetic studies to date have focused on candidate variants, with sparse findings. We aimed to perform the first mitochondrial genome-wide association study of migraine, examining both single variants and mitochondrial haplogroups. Methods In total, 71,860 participants from the population-based Nord-Trøndelag Health Study were genotyped. We excluded samples not passing quality control for nuclear genotypes, in addition to samples with low call rate and closely maternally related. We analysed 775 mitochondrial DNA variants in 4021 migraine cases and 14,288 headache-free controls, using logistic regression. In addition, we analysed 3831 cases and 13,584 controls who could be reliably assigned to a mitochondrial haplogroup. Lastly, we attempted to replicate previously reported mitochondrial DNA candidate variants. Results Neither of the mitochondrial variants or haplogroups were associated...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial genome-wide association study of migraine – the HUNT Study","attachmentId":84816307,"attachmentType":"pdf","work_url":"https://www.academia.edu/77496492/Mitochondrial_genome_wide_association_study_of_migraine_the_HUNT_Study","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/77496492/Mitochondrial_genome_wide_association_study_of_migraine_the_HUNT_Study"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="8985463" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/8985463/Quantitative_pedigree_analysis_and_mitochondrial_DNA_sequence_variants_in_adults_with_cyclic_vomiting_syndrome">Quantitative pedigree analysis and mitochondrial DNA sequence variants in adults with cyclic vomiting syndrome</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="3070540" href="https://usc.academia.edu/EssamZaki">Essam Zaki</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Abstract Background Children with cyclic vomiting syndrome (CVS) have a high degree of maternal inheritance of functional gastrointestinal and neurological disorders. CVS in children is also associated with an increased prevalence of mitochondrial DNA single-nucleotide polymorphisms (mtDNA SNPs) 16519 T and 3010A. Preliminary data suggests that age of onset of symptoms (pediatric vs. adult) may be a determinant of the presence of such mtDNA SNP’s. We sought to examine the degree of maternal inheritance pattern of functional disorders and the prevalence of mtDNA SNP’s16519T and 3010A in adults with CVS and correlate this with age of onset of disease. Methods A Quantitative Pedigree Analysis (QPA) was performed in 195 of a total of 216 patients and all were genotyped using Restriction Fragment Length Polymorphism (RFLP) or sequencing. Results Adults with CVS had a higher degree of probable maternal inheritance (PMI) of functional disorders than controls (12% vs. 1%, p < 0.001). However, the prevalence of mitochondrial SNP’s 16519 T, 3010A and the AT genotype were similar in Haplogroup H CVS patients compared to historical controls. There was no correlation between age of onset of disease and prevalence of these mtDNA SNP’s. Conclusions A subset of adults with CVS has a significantly higher degree of maternal inheritance pattern of functional disorders than controls. There was no association with mtDNA SNP’s 16519 T and 3010A as seen in children and future studies sequencing the entire mitochondrial and nuclear genome to identify potential causes for this maternal inheritance pattern in adults are warranted.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Quantitative pedigree analysis and mitochondrial DNA sequence variants in adults with cyclic vomiting syndrome","attachmentId":35299116,"attachmentType":"pdf","work_url":"https://www.academia.edu/8985463/Quantitative_pedigree_analysis_and_mitochondrial_DNA_sequence_variants_in_adults_with_cyclic_vomiting_syndrome","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/8985463/Quantitative_pedigree_analysis_and_mitochondrial_DNA_sequence_variants_in_adults_with_cyclic_vomiting_syndrome"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":53554929,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":53554929,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_53554929" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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data-author-id="3070540" href="https://usc.academia.edu/EssamZaki">Essam Zaki</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Mitochondrion, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"51 A common mtDNA control region polymorphism 16519T is associated with migraine without aura and cyclic vomiting","attachmentId":50650024,"attachmentType":"pdf","work_url":"https://www.academia.edu/2380360/51_A_common_mtDNA_control_region_polymorphism_16519T_is_associated_with_migraine_without_aura_and_cyclic_vomiting","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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ds2-5-body-xs">Journal of affective disorders, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial inheritance in depression, dysmotility and migraine?","attachmentId":76503267,"attachmentType":"pdf","work_url":"https://www.academia.edu/64491321/Mitochondrial_inheritance_in_depression_dysmotility_and_migraine","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/64491321/Mitochondrial_inheritance_in_depression_dysmotility_and_migraine"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" 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ds2-5-body-xs">neurogenetics, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred","attachmentId":44540609,"attachmentType":"pdf","work_url":"https://www.academia.edu/24209581/Familial_hemiplegic_migraine_linkage_to_chromosome_14q32_in_a_Spanish_kindred","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/24209581/Familial_hemiplegic_migraine_linkage_to_chromosome_14q32_in_a_Spanish_kindred"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 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