线粒体DNA异质性的变异性：与无症状性颈动脉粥样硬化的关联

Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis.

作者信息

Sazonova Margarita A, Kirichenko Tatiana V, Ryzhkova Anastasia I, Sazonova Marina D, Doroschuk Natalya A, Omelchenko Andrey V, Nikiforov Nikita G, Ragino Yulia I, Postnov Anton Yu

机构信息

Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia.

Laboratory of Medical Genetics, Institute of Experimental Cardiology, Chazov National Medical Research Center of Cardiology, 15a, 3rd Cherepkovskaya Str., Moscow 121552, Russia.

出版信息

Biomedicines. 2024 Aug 15;12(8):1868. doi: 10.3390/biomedicines12081868.

DOI:10.3390/biomedicines12081868

PMID:39200332

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11351276/

Abstract

Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west-east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region.

摘要

动脉粥样硬化是心血管疾病发展的主要原因之一。本研究旨在分析新西伯利亚地区动脉粥样硬化患者和条件健康的研究参与者的颈动脉中mtDNA突变与动脉粥样硬化斑块之间的关联。对包含10个研究的mtDNA突变区域的DNA的PCR片段进行焦磷酸测序。使用基于M. A. Sazonova及其同事开发的焦磷酸测序技术的定量方法分析mtDNA突变的异质性水平。在对新西伯利亚地区颈动脉有动脉粥样硬化斑块的患者样本和条件健康的研究参与者进行分析时，检测到线粒体基因组中的四个促动脉粥样硬化突变（m.5178C>A、m.652delG、m.12315G>A和m.3256C>T）以及mtDNA中的三个抗动脉粥样硬化突变（m.13513G>A、m.652insG和m.14846G>A）。在mtDNA突变m.5178C>A、m.3256C>T、m.652insG和m.13513G>A的分布中发现了一个西-东梯度。因此，在新西伯利亚地区颈动脉有动脉粥样硬化斑块的患者中检测到线粒体基因组中的四个促动脉粥样硬化突变（m.5178C>A、m.652delG、m.12315G>A和m.3256C>T）以及mtDNA中的三个抗动脉粥样硬化突变（m.13513G>A、m.652insG和m.14846G>A）。