Abstract 563: Whole Mitochondrial Genome Association Analysis Of Essential Hypertension In Chinese General Population

Abstract

Objective: Genetic studies of essential hypertension have mainly focused on the genome-wide association study of nuclear genes, which could explain just a small fraction of the heritability of blood pressure traits. This study aimed to investigate the relationship between mitochondrial genetic variants and essential hypertension (EH) in Chinese general population. Methods: Demographic and clinical matched 100 pairs of Chinese-Han EH patients and controls were recruited in the derivation cohort. A total of 797 EH patients and 816 controls were recruited in the derivation cohort. DNA was extracted from the peripheral whole blood of each patient. The whole mitochondrial genome was re-sequenced in the derivation cohort. The screened related variants were genotyped in the derivation cohort. Association analysis was performed to identify EH related variants. Results: In the derivation cohort, a total of 537 variants were detected in mitochondrial genome with 29 in tRNA-coding genes, 45 in rRNA-coding genes, 10 in D-Loop functional regions, and 453 in protein-encoded genes. No statistical difference could be found between EH patients and controls for the distribution of t-RNA, r-RNA and D-loop variants. For the protein-encoded genes, compared with controls, the occurrence of ND2 C5178A genetic variant was significantly lower [18% (18 in 100) vs. 31% (31 in 100), P = 0.03] in EH cases. Similarly, the distribution of C8414T of ATP8 gene in EH cases was significantly lower(10% vs. 22%, P = 0.02)than that in controls. No other mitochondrial variant exhibited significantly different distribution between EH cases and controls in the derivation cohort. The significant protective roles of ND2 and ATP8 genetic variants on EH were confirmed in the validation cohort (For ND2 C5178A: 24.59% (196 in 797) in EH vs. 32.72% (267 in 816) in control; adjusted OR: 0.62, 95% CI: 0.49-0.79, P < 0.001; For ATP8 C8414T: 17.69% (141 in 797) in EH vs. 23.16% (189 in 816) in control; adjusted OR: 0.68, 95% CI: 0.52-0.89, P = 0.005). Conclusion: This study provides the evidence that mitochondrial genetic variants of C5178A in ND2 gene and C8414T in ATP8 gene may exert protective role against EH in Chinese general population.