背景:中风,全球第二大死因,是一种复杂的疾病,受许多危险因素的影响,我们可以在其中找到活性氧(ROS)。由于线粒体是细胞ROS的主要生产者,如今,研究试图阐明这些细胞器及其DNA(mtDNA)变异在卒中风险中的作用。本研究的目的是对mtDNA突变和mtDNA含量与卒中风险之间的关系进行综合评估。
方法:在一项病例对照研究中,使用110例中风患者及其相应的对照个体,分析了mtDNA的同质和异质突变。在73个病例对照对中分析了线粒体DNA拷贝数(mtDNA-CN)。
结果:我们的结果表明单倍群V,特别是变体m.72C>T,m.4580G>A,m.15904C>T和m.16298T>C对卒中风险有保护作用。相反,变体m.73A>G,m.11719G>A和m.14766C>T似乎是卒中的遗传危险因素。在这项研究中,我们发现卒中风险与线粒体DNA拷贝数之间无统计学显著关联.
结论:这些结果证明了mtDNA遗传学在卒中发病机制中的可能作用,可能是通过线粒体ROS产生的改变。
Stroke, the second leading cause of death worldwide, is a complex disease influenced by many risk factors among which we can find reactive oxygen species (ROS). Since mitochondria are the main producers of cellular ROS, nowadays studies are trying to elucidate the role of these organelles and its DNA (mtDNA) variation in stroke risk. The aim of the present study was to perform a comprehensive evaluation of the association between mtDNA mutations and mtDNA content and stroke risk.
Homoplasmic and heteroplasmic mutations of the mtDNA were analysed in a
case-controls study using 110 S cases and their corresponding control individuals. Mitochondrial DNA copy number (mtDNA-CN) was analysed in 73 of those
case-control pairs.
Our results suggest that haplogroup V, specifically variants m.72C > T, m.4580G > A, m.15904C > T and m.16298 T > C have a protective role in relation to stroke risk. On the contrary, variants m.73A > G, m.11719G > A and m.14766C > T appear to be genetic risk factors for stroke. In this study, we found no statistically significant association between stroke risk and mitochondrial DNA copy number.
These results demonstrate the possible role of mtDNA genetics on the pathogenesis of stroke, probably through alterations in mitochondrial ROS production.