No Evidence of Association Between Common European Mitochondrial DNA Variants in Alzheimer, Parkinson, and Migraine in the Spanish Population
No Evidence of Association Between Common European Mitochondrial DNA Variants in Alzheimer, Parkinson, and Migraine in the Spanish Population
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DOI：
10.1002/ajmg.b.32276
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Salas, Antonio
中科院分区：
文献类型：
--
作者：
Fachal, Laura;Mosquera-Miguel, Ana;Salas, Antonio
某些线粒体DNA(MtDNA)变异和单倍群已被发现与神经疾病有关。一些研究表明，线粒体DNA变异可能通过影响高能量需求器官(如大脑)的ATP产生，在这些疾病中起到病因学作用。我们分析了五组阿尔茨海默病(AD)、帕金森病(PD)和偏头痛患者以及对照组的15个mtDNA SNPs(MtSNPs)，以评估mtDNA变异在疾病风险中的作用。对mtSNPs和线粒体单倍群进行了关联测试。在AD和PD队列中没有发现任何mtSNP或单倍组的显著关联。校正T4216C和G13708A和单倍组J(FDR Q值=0.02；圣地亚哥队列)后，两个mtSNPs与一个偏头痛队列相关。然而，这种关联在第二个复制型偏头痛系列中并未得到证实。回顾文献发现，存在不一致的发现和方法上的缺陷，影响了很大一部分关于AD、PD和偏头痛的线粒体DNA关联研究。对文献的详细检查突出表明，需要在线粒体DNA遗传关联研究中执行更严格的方法学和统计标准，以避免线粒体DNA变异与神经系统疾病之间关联的假阳性结果。(C)2014年威利期刊公司。
Certain mitochondrial DNA ( mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases. (C) 2014 Wiley Periodicals, Inc.