Haplotype of the mutations m.3256С>Т, m.12315G>A, m.13513A>G and m.15059G>A mitochondrial genome associated with phenotypic expression of the predisposition to atherosclerotic lesions

Abstract

Mitochondrial genome mutations haplotypes associated with phenotypic manifestations of predisposition to atherosclerotic lesions were identified. The data suggests the existence of several «haplotypes» mitochondrial mutations associated with an increased risk of atherosclerosis. To formulate names оf mitochondrial genome «haplotypes» the principle of individual heteroplasmy indicators relative to the mid-point was used. The median value for heteroplasmy level of mutations m.3256С>Т amounted to 17.5%, mutation m.12315G>A — 28%, mutation m.13513G>A — 19.5%, and mutation m.15059G>A — 39%. On the basis of the estimated degree of genetic risk (CPEM) most small and meaningful options for aggregate mutations m.3256С>Т, m.12315G>A, m.13513A>G and m.15059G>A are «haplotype» CGAG (lowest susceptibility to atherosclerosis) and TAGA (the greatest susceptibility to atherosclerosis) respectively; other possible combinations are intermediate. Prevailing anti-atherosclerotic haplotype CGAG and CGGG met at 21.3% of survey participants. The prevailing proatherosclerotic haplotype TAAA, TAGG and TAGA met at 44.8% of survey participants. 2/3 of these haplotypes are associated with increased risk of atherosclerosis. Approximate extent of the genetic risk of mitochondrial «haplotype» on mutations, m.3256С>Т, m.12315G>A, m.13513A>G and m.15059G>A and linearly related to absolute thickness intimo-medial layer of the carotid arteries and the manifestation of atherosclerotic plaques in the surveyed group of persons-participants of experimental clinical studies. The purpose. Find an association between atherosclerosis manifestations (TIMS, plaques) and gapoltipami mutations of the mitochondrial genome. Methods. The object of the research were 130 people: patients with coronary artery disease who underwent myocardial infarction, patients with ultrasound evidence of atherosclerosis, and relatively healthy, with no ultrasound evidence of atherosclerosis. The material of the studies were DNA samples isolated from blood cells collected from study participants. DNA extraction was performed with phenol-chloroform method. The isolated DNA was used to determine the percentage of mitochondrial heteroplasmy 9 mutations using PCR in real time. Results. Нaplotypes of mutations of the mitochondrial genome have been identified associated with the phenotypic manifestations of susceptibility to atherosclerotic lesions. The prevailing anti-atherosclerotic and haplotypes CGAG CGGG occurred in 21.3% of study participants. Prevailing atherosclerotic haplotypes TAAA, TAGG and TAGA occurred in 44.8% of study participants. Thus, it was found that there are a few common haplotypes of mutations of the mitochondrial genome, covering about 65% of the population; 2/3 of these haplotypes is associated with increased susceptibility to atherosclerosis. Conclusion. The results indicate that the presumed degree of genetic risk of mitochondrial «haplotype» for mutations m.3256С>Т, m.12315G>A, m.13513A>G and m.15059G>A is linearly related to the absolute thickness of intima-media layers of the carotid arteries and the severity of atherosclerotic plaques in the studied group of persons — participants of experimental and clinical studies.