Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the co...Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.展开更多
AIM: To examine whether the heteroplasmy level for 15059G】A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participant...AIM: To examine whether the heteroplasmy level for 15059G】A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Ath-erosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G】A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS: The 15059G】A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G】A heteroplasmy distribution, significant differences were observed for patients’ age, systolic blood pressure, and triglyceride levels. 15059G】A heteroplasmy correlated both with age (r = 0.331, P 【 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G】A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G】A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G】A heteroplasmy level were found to have significantly higher age (P 【 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G】A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G】A heteroplasmy and essential hypertension. CONCLUSION: This study provides the evidence of association of mtDNA 15059G】A mutation heteroplasmy with essential hypertension.展开更多
基金Supported by The Russian Ministry of Science and Education
文摘Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.
基金Supported by The Russian Ministry of Science and Education
文摘AIM: To examine whether the heteroplasmy level for 15059G】A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Ath-erosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G】A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS: The 15059G】A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G】A heteroplasmy distribution, significant differences were observed for patients’ age, systolic blood pressure, and triglyceride levels. 15059G】A heteroplasmy correlated both with age (r = 0.331, P 【 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G】A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G】A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G】A heteroplasmy level were found to have significantly higher age (P 【 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G】A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G】A heteroplasmy and essential hypertension. CONCLUSION: This study provides the evidence of association of mtDNA 15059G】A mutation heteroplasmy with essential hypertension.
