The pathogenesis of atherosclerosis and ischemic heart disease is associated with oxidative stress and mitochondrial dysfunction. Mitochondrial DNA encodes subunits of mitochondrial respiratory chain and is highly polymorphic in human populations. Mitochondrial DNA can be considered a candidate genetic locus for predisposition to cardiovascular diseases.Aim. To analyze the associations of the mitochondrial genome polymorphism and chronic heart failure in ischemic heart disease.Material and Methods. The study included two groups of individuals: patients with a combination of ischemic heart disease and chronic heart failure (n = 175) and a population sample of residents of Tomsk (n = 424). Percentages of patients with chronic heart failure of NYHA classes II, III, and IV were 37%, 50%, and 13%, respectively. All patients underwent echocardiographic examination; body mass index and the lipid fractions in blood serum were determined. The average was 55.4 years in patients and 47.6 years in the population sample. Polymorphism of mtDNA was studied by sequencing the hypervariable segment of D-loop of mtDNA and subsequent classification of mtDNA haplotypes into the known haplogroups. The mtDNA haplogroup frequencies were compared between the samples using the Chi-square test. The associations of genotype with quantitative trait variability were analyzed by variance analysis.Results. Male patients showed a higher frequency of haplogroup H compared to the population (45.86% in patients and 35.4% in population) and a higher total frequency of haplogroup H subgroups except the most frequent subgroup H1 (36.94% and 25.22%, respectively). The values of significance level (p-value) and odds ratio (OR) were determined as follows: p = 0.04; odds ratio OR = 1.55 (95% confidence interval (CI) 1.02–2.34) for haplogroup H as a whole; p = 0.02; OR = 1.74 (95% CI 1.12–2.70) for haplogroup H without subgroup H1. Analysis of quantitative traits revealed the associations of the same genetic marker (mtDNA haplogroup H) with the levels of high-density lipoproteins (p = 0.03) and triglycerides (p = 0.02) in blood serum of men in the population sample.Conclusion. The obtained results suggested that the most frequent European mtDNA haplogroup H may be a risk factor for the complications of ischemic heart disease in men.
Митохондриальный геном кодирует жизненно важные белки субъединиц дыхательной цепи и характеризуется высоким уровнем полиморфизма в популяциях человека. Однако работы по поиску генов предрасположенности к многофакторным заболеваниям, в том числе сердечно-сосудистым, часто ограничиваются анализом ядерного генома. В то же время показано, что отдельные генотипы мтДНК могут отличаться более высокой или низкой эффективностью окислительного фосфорилирования. Выявлены ассоциации популяционного полиморфизма мтДНК с сердечно-сосудистыми заболеваниями. Согласно результатам наших исследований, а также опубликованных другими авторами результатам ассоциативных и функциональных исследований, можно говорить о том, что эффект полиморфизма мтДНК проявляется чаще не в предрасположенности к сердечно-сосудистым заболеваниям в целом, а в риске развития осложнений и коморбидных фенотипов в пределах синтропии сердечно-сосудистого континуума. Mitochondrial genome, encoding respiratory chain subunits, is characterized by high polymorphism level in human populations. In most studies for susceptibility genes for common diseases, including cardiovascular diseases, the analysis is limited to the nuclear genome. It was shown that particular mtDNA genotypes may differ by oxidative phosphorylation efficiency. Some associations of mtDNA polymorphisms with cardiovascular diseases have been found. According to our results and published data, we suggest that mtDNA effect on cardiovascular system does not manifest in predisposition to cardiovascular diseases themselves but rather in risk of complications and comorbidities in the cardiovascular continuum.
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