No Evidence of Association Between Common European Mitochondrial DNA Variants in Alzheimer, Parkinson, and Migraine in the Spanish Population

作者：Fachal Laura; Mosquera Miguel Ana; Pastor Pau; Ortega Cubero Sara; Lorenzo Elena; Oterino Duran Agustin; Toriello Maria; Quintans Beatriz; Camina Tato Montse; Sesar Angel; Vega Ana; Sobrido Maria Jesus; Salas Antonio^*

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2015, 168(1): 54-65.

DOI：10.1002/ajmg.b.32276

• mitochondrial DNA
• SNPs
• association studies
• population stratification
• false positive
• Parkinson disease
• Alzheimer disease
• migraine

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.

• 出版日期2015-1