Genetic and functional features of peripheral blood leukocyte mitochondria in patients with coronary heart disease and high risk of sudden cardiac death

Aim. To assess the relationship between the respiration of mitochondria of peripheral blood leukocytes and mitochondrial DNA (mtDNA) polymorphism in patients with coronary heart disease (CHD) depending on the risk of developing sudden cardiac death (SCD).Materials and methods. We formed two groups of patients: the main group - patients with CHD and the high risk of SCD (n = 107); the comparison group - patients with stable course of CHD without the risk of SCD (n = 50). Using methods of high-throughput sequencing, we determined patients’ haplogroup and carriage of mtDNA polymorphisms A2706G, G3010A and G9055A. The respiratory activity of isolated mitochondria from peripheral blood leukocytes was assessed by amperometric method using NADand FAD-dependent oxidation substrates.Results. In both studied groups, H, U, and J haplogroups were predominant (74.5% and 92.5%, respectively, for the main group and the comparison group). There were more minor haplogroups in the main group than in the comparison group. The frequencies of occurrence of polymorphisms A2706G, G3010A, and G9055A did not significantly differ between the groups. In the main group, carriage of the A2706G polymorphism was associated with a decrease in the respiratory control ratio (RC) in FAD-dependent respiration (p = 0.05), and in the comparison group it was associated with a decrease in oxygen consumption rate (OCR) in the V4 metabolic state in both NADand FAD-dependent respiration (p = 0.002 and p = 0.008, respectively) without changing in RC. In the main group, carriage of the G9055A polymorphism was associated with a decrease in OCR in the V3 metabolic state (p = 0.037) in FAD-dependent respiration. For the G3010A polymorphism, no association with mitochondrial respiration was found in the studied groups.Conclusion. In patients with CHD, regardless of the risk of SCD, the frequencies of haplogroups H, U, and J and mtDNA polymorphisms A2706G, G3010A, and G9055A do not differ significantly. In patients with high risk of SCD, carriage of the A2706G polymorphism is associated with a decrease in RC in FAD-dependent respiration, and the G9055A polymorphism is associated with a decrease in OCR in V3 during FAD-dependent respiration.

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