室性心动过速患者线粒体DNA基因罕见错义替换。

IF 1 Q3 AGRICULTURE, MULTIDISCIPLINARY
M V Golubenko, N P Babushkina, V A Korepanov, N R Valiakhmetov, T A Atabekov, K N Vitt, A A Zarubin, O A Makeeva, S A Afanasiev, R E Batalov, A A Garganeeva, M S Nazarenko, V P Puzyrev
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引用次数: 0

摘要

人类线粒体DNA (mtDNA)具有高度的群体多态性。虽然已知某些致病性mtDNA变异可引起遗传性线粒体综合征,通常表现为心律失常,但危及生命的室性心动过速(VT)本身是心血管疾病猝死的主要危险因素。这项工作的目的是研究有记录的室性心动过速发作患者与没有危及生命的心律失常的缺血性心脏病患者和没有心血管疾病临床表现的个体的mtDNA中罕见的(“私人”)错义替换。mtDNA测序采用高通量测序方法。预测基因变异影响的专门算法被用来评估错义替换的影响。对所鉴定的氨基酸置换谱的比较分析表明,三组中约有40%的个体是mtDNA“私有”错义变体的携带者。然而,在这些替换中,APOGEE2预测因子分类为“不确定意义变异”(VUS)的变异在心律失常患者组中比在对照组中更常见,在对照组中未检测到VUS类别的“私人”错义替换(Fisher精确检验p = 0.0063)。此外,两组在phrd -rank组合注释依赖消耗(CADD)得分上存在差异,对照组个体的CADD得分较低。结果表明,罕见的mtDNA变异可能有助于心血管疾病的易感性,特别是一些患者发生室性心动过速的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rare missense substitutions in the mitochondrial DNA genes in patients with ventricular tachycardia.

Human mitochondrial DNA (mtDNA) exhibits high population-level polymorphism. While certain pathogenic mtDNA variants are known to cause hereditary mitochondrial syndromes, often presenting with cardiac arrhythmias, life-threatening ventricular tachycardia (VT) itself is a major risk factor for sudden death in cardiovascular diseases. The aim of the work was to study rare ("private") missense substitutions in the mtDNA of patients with documented episodes of ventricular tachycardia in comparison with patients with ischemic heart disease without life-threatening heart arrhythmias and individuals without clinical manifestations of cardiovascular diseases. The sequencing of mtDNA was performed using high-throughput sequencing methods. Specialized algorithms predicting the effect of gene variants were used to assess the effect of missense substitutions. Comparative analysis of the spectrum of the identified amino acid substitutions in the studied groups showed that about 40 % of the individuals in all three groups were carriers of "private" missense variants in mtDNA. However, among such substitutions, the variants classified by the APOGEE2 predictor as "variants of uncertain significance" (VUS) were more common in the group of patients with heart arrhythmias than in the control group, where "private" missense substitutions of the VUS category were not detected (p = 0.0063 for Fisher's exact test). In addition, the groups differed in their phred-ranked Combined Annotation Dependent Depletion (CADD) scores, which were lower for individuals in the control group. The results indicate that rare mtDNA variants may contribute to predisposition to cardiovascular disease - in particular, to the risk of developing ventricular tachycardia by some patients.

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来源期刊
Vavilovskii Zhurnal Genetiki i Selektsii
Vavilovskii Zhurnal Genetiki i Selektsii AGRICULTURE, MULTIDISCIPLINARY-
CiteScore
1.90
自引率
0.00%
发文量
119
审稿时长
8 weeks
期刊介绍: The "Vavilov Journal of genetics and breeding" publishes original research and review articles in all key areas of modern plant, animal and human genetics, genomics, bioinformatics and biotechnology. One of the main objectives of the journal is integration of theoretical and applied research in the field of genetics. Special attention is paid to the most topical areas in modern genetics dealing with global concerns such as food security and human health.
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