Abstracts

Recently, it has been shown that dysfunction of mitochondria is an important component of the molecular mechanisms of the development of many neurodegenerative diseases. These include multiple sclerosis, a chronic autoimmune and neurodegenerative disease of the central nervous system, which is characterized by clinical heterogeneity. The role of genetic variability of mitochondrial DNA in the development of various clinical forms of multiple sclerosis is poorly understood. The aim of present study was to analyze the association of ten mitochondrial DNA single nucleotide polymorphisms and the nine most common European mitochondrial haplogroups (H, J, K, U, T, I, V, W and X) with a severe and relatively rare multiple sclerosis disease form—primary progressive multiple sclerosis. 110 patients with primary progressive multiple sclerosis and 406 healthy controls were enrolled in the study, all ethnic Russians. For the first time association of the m.12308*G (rs2853498) variant (P = 0.024) and haplogroup U (P = 0.0004, passes the adjustment for multiple comparisons: P_corr = 0.0076) with primary progressive multiple sclerosis was shown. Comparison of these data with the results of our previous study [1], that was focused on the role of mitochondrial genome variability in susceptibility to the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis, leads to the conclusion that two different mitochondrial haplogroups, U and J, are involved in the development of two different clinical forms of multiple sclerosis. The results may contribute to the identification of new targets for the treatment of primary progressive multiple sclerosis, for which there is no effective pathogenetic treatment at the moment.

中文翻译：

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线粒体基因组的变异性和多发性硬化症的主要进展形式的发展

摘要

最近，已经表明线粒体功能障碍是许多神经退行性疾病发展的分子机制的重要组成部分。其中包括多发性硬化症，中枢神经系统的慢性自身免疫性疾病和神经退行性疾病，其特征是临床异质性。线粒体DNA遗传变异性在多发性硬化症的各种临床形式的发展中的作用了解甚少。本研究的目的是分析十种线粒体DNA单核苷酸多态性与九种最常见的欧洲线粒体单倍群（H，J，K，U，T，I，V，W和X）的关联，这些关联与严重且相对罕见多发性硬化症疾病形式-原发性进行性多发性硬化症。这项研究招募了110名原发性进行性多发性硬化症患者和406名健康对照者，所有俄罗斯人。首次关联m.12308 * G（rs2853498）变体（P = 0.024）和单倍体U（P = 0.0004，通过多次比较的校正：P _corr = 0.0076）显示为原发性进行性多发性硬化症。将这些数据与我们先前的研究结果进行比较[1]，后者的研究重点在于线粒体基因组变异在对最常见形式的多发性硬化症（复发-缓解型多发性硬化症）的易感性中的作用，得出以下结论：两种不同的线粒体U和J单倍群参与了两种不同形式的多发性硬化症的临床发展。结果可能有助于确定治疗原发性进行性多发性硬化症的新目标，目前尚无有效的病原学治疗方法。