Objectives: To evaluate the association between the level of heteroplasmy for mitochondrial mutations C3256T, G13513A, G14846A, G12315A in human white blood cells and presence of atherosclerosis in coronary and carotid arteries. Methods: We included 130 patients (mean age 55±9 years, 116 men) with coronary heart disease (CHD) verified by angiography. Control group consisted of 63 subjects without angiographic coronary artery disease. Carotid artery duplex scan was performed to evaluate the extent and severity of carotid atherosclerosis. DNA samples were obtained from whole venous blood using commercially available kits for DNA extraction. For the amplification of fragments of mitochondrial DNA by polymerase chain reaction method followed by pyrosequencing, the corresponding primers and conditions were used. On the basis of pyrosequencing data analysis, the level of heteroplasmy forC3256T, G13513A, G14846A, G12315Amutations in DNA samples were calculated. Results: The level of G13513A and C3256T heteroplasmy was significantly higher (p=0.03; p=0.01, respectively) and level of G12315A heteroplasmy was lower (p=0.004) in CHD patients versus control group. There was significant correlation of carotid atherosclerosis severity and levels of ? 3256? (r=0.49, p=0.0001), G14846A (r=0.48, p=0.0001) and G12315A heteroplasmy (r=-0.32, p=0.01). Level of G13513A, G14846A heteroplasmy was higher in subjects older than 45 years. There was no any relation of mitochondrial genome mutations and smoking, hypertension, CHD family history, obesity. Presence of hyperlipidemia was positively related to C3256T heteroplasmy (r=0.18, p=0.01) and negatively associated with G12315A heteroplasmy (r= -0,2, ?=0,005). There was positive significant correlation between lipoprotein(a) level and G14846A (r= 0,23, ?=0,01). Conclusion: In this case-control study we found independent positive correlation of mitochondrial genome mutations ?3256T, G13513A and G14846A with both coronary and carotid atherosclerosis, whereas there was a negative relationship with G12315A. Our findings indicate that these mitochondrial DNA mutations could serve as predisposing markers of genetic susceptibility for atherosclerosis development.
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