A coding polymorphism of the kallikrein 1 gene is associated with essential hypertension: a tagging SNP-based association study in a Chinese Han population

Objective The aim of this study was to investigate the association between common variants in the human tissue kallikrein 1 (KLK1) gene and susceptibility to essential hypertension in Chinese Han. Methods A tagging single nucleotide polymorphism (tSNP) approach was used for a case-control study in 2411 patients with essential hypertension and 2348 controls. All DNA samples and clinical data were collected from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). Results Based on the HapMap data of Han Chinese in Beijing (CHB) population, two non-synonymous polymorphisms, namely rs5517 (Glu162Lys) and rs5516 (Gin121 Glu), were selected as tSNPs which could efficiently tag eight SNPs of the KLK1 gene with R-2 larger than 90% for both haplotypes and single locus. Significant differences were found between groups for frequencies of rs5517 A allele (42.48% in cases versus 39.32% in controls, P = 0.0019) and AA genotype [adjusted odds ratio (OR)= 1.25 for AA versus AG/GG, P = 0.0067]. The haplotype composed of the rs5517 A and rs5516 G allele significantly increased the risk of hypertension, with adjusted OR of 1.12 [95% confidence interval (Cl), 1.04-1.28, P = 0.0377] when compared with the common haplotype G-C. Diplotype analysis also showed a significant association between the diplotype of AG-AC and essential hypertension (OR= 1.34, 95% Cl, 1.07-1.68, P = 0.0096). Conclusions The present study suggested that rs5517 in the KLK1 gene was significantly associated with essential hypertension in a Chinese Han population.