Gender-specific association between the kininogen 1 gene variants and essential hypertension in Chinese Han population.

Background: Kininogens serve as the precursors of potent vasoactive kinin peptides and also function as cysteine proteinase inhibitors.

Method: Given its potential role in blood pressure homeostasis, a tagging single nucleotide polymorphism (SNP) based case-control study was conducted to explore the association between kininogen 1 gene common variants and essential hypertension in Chinese Han population. Four tagging SNPs were selected on the basis of the HapMap database and further genotyped in 2411 patients with essential hypertension and 2348 controls from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China).

Results: A significant gender-specific association between the kininogen 1 gene common variants and essential hypertension was observed. In male, but not female participants, rs2304456 CC genotype and rs4686799 TT genotype were significantly related to hypertension [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.24-3.90, P = 0.007 and OR = 1.31, 95% CI: 1.04-1.66, P = 0.025, respectively]. The haplotypes G-C-C-T and the A-A-T-T were significantly associated with essential hypertension in the male population with adjusted OR 1.43 (P < 0.001) and OR 1.24 (P = 0.001), respectively. The haplotype G-A-C-T was in significant association with essential hypertension (OR = 1.42, P = 0.003) as well as systolic blood pressure (P = 0.005) and diastolic blood pressure (P = 0.015).

Conclusion: This is the first association study of the kininogen 1 gene with essential hypertension. Both single-locus and haplotype analyses indicated the kininogen 1 gene was associated with essential hypertension and blood pressure traits in the Chinese male population.