ASSOCIATION OF MUTATIONS IN THE MITOCHONDRIAL GENOME WITH CORONARY AND CAROTID ATHEROSCLEROTIC LESIONS

Objective: to study the association of C3256T, G13 513A, G14 846A, and G12 315A mutations in the mitochondrial genome with the presence and degree of coronary and carotid atherosclerotic lesions.

Subjects and methods. The investigation enrolled 193 patients (mean age 54.6 ± 9.5 years), including 154 men, who had undergone coronary angiography. A study group consisted of 130 patients with coronary atherosclerosis. A control group comprised 63 patients without this disease. Genetic analysis consisted of 3 steps: 1) isolation of genomic deoxyribonucleic acid from whole blood leukocytes by phenol-chloroform extraction; 2) amplification of polymorphic sites in the examined mitochondrial deoxyribonucleic acid genes by polymerase chain reaction; 3) pyrosequencing
for the detection of nucleotide sequencing and the determination of the level of heteroplasmy of the examined mutations.

Results. The level of heteroplasmy of G13 513A and C3256T mutations was statistically significantly higher in the patients with coronary atherosclerosis than in those without this condition (p = 0.03 and p = 0.01, respectively) whereas that of G12 315A mutation was significantly higher in the persons without coronary atherosclerosis (p = 0.004). The level of heteroplasmy of G14 846A mutation was greater in people over 45 years of age. No association was found between mutations in the mitochondrial genome and cardiovascular risk factors, such as smoking, hypertension, poor family history, and obesity. There was a direct relationship of hyperlipidemy to C3256T mutation (r = 0.18; р = 0.01) and its inverse relationship to G12 315A mutation (r = –0.2; р = 0.005), There was a positive correlation between G14 846A mutation
and lipoprotein (a) levels. There was also a positive correlation between carotid atherosclerosis with С3256Т (r = 0.49; p = 0.0001)
and G14 846A (r = 0.48; p = 0.0001) mutations. G12 315A mutation showed a negative correlation with carotid atherosclerosis (r = –0.32; p = 0.01). 

Conclusion. The case-control study gave proof to the association between the level of heteroplasmy of С3256T, G13 513A, G14 846A, and G12 315A mutations in the mitochondrial genome and coronary and carotid atherosclerosis. Measurement of the heteroplasmy of С3256T, G13 513A and G14 846A mutations in the mitochondrial gene may be proposed as potential genetic markers to improve the diagnosis of a preposition to coronary and carotid atherosclerosis.

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