Abstract 562: Association Of The Heteroplasmic Level Of The Mitochondrial Gene Nd2 5178c>A Variant With Essential Hypertension

Abstract

BACKGROUND: The mitochondrial genetic variant of nicotinamide adenine dinucleotide dehydrogenase subunit-2 (ND2) 5178C>A (Leu237Met) was previously found to have a protective effect against essential hypertension (EH) in Chinese and Japanese populations. AIM: The present study aimed to determine whether the protective effect of ND2 5178C>A against EH is associated with the mitochondrial heteroplasmy level of the variant. METHODS: This case-control study involved 109 unrelated Chinese-Han matched pairs of essential hypertension and healthy normotensive controls. All consented subjects were recruited consecutively from Institute of Geriatric Cardiology and Health Examination Center in General Hospital of Chinese People’s Liberation Army from February 2013 to January 2014. Demographic and clinical characteristics were recorded. Mitochondrial DNA was isolated from the blood leukocytes for each subject. The level of heteroplasmy for 5178C>A variant occurring in the coding region of ND2 was quantified using real-time polymerase chain reaction (PCR) method. RESULTS: The ND2 5178C>A heteroplasmy level ranged between 27% and 77%, with a median level of 44%. Between the upper and lower quartiles of 5178C>A heteroplasmy distribution, significant differences were observed for systolic blood pressure (116±17 vs. 129±25 mmHg, P=0.004) , body mass index (BMI) (24.6±3.3 vs.26.5±3.6, P=0.008) , total cholesterol (4.0±0.8 vs. 3.4±0.9 mmol/L, P<0.001) , low density lipoprotein (2.5±0.7 vs. 1.5±0.7 mmol/L, P<0.001) and triglyceride levels (1.8±1.6 vs. 4.0±1.6 mmol/L, P<0.001). ND2 5178C>A heteroplasmic level was negatively correlated with the presence of hypertension (r = -0.38, P < 0.001), BMI (r = -0.19, P = 0.007), and the level of total cholesterol (r = -0.18, P = 0.01). Logistic regression analysis showed that participants with higher ND2 5178C>A heteroplasmy level (≥44%) were found to have significantly lower prevalence of essential hypertension (29%, 32 in 109), as compared to those with lower (< 44%) ND2 5178C>A heteroplasmy level (71%, 77 in 109) (OR: 0.18, 95% CI: 0.10-0.31, P<0.001). CONCLUSION: The protective effect of mitochondrial ND2 5178C>A against EH is associated with the heteroplasmy level of the variant.