Sex-specific Association of Rs4746172 of VCL Gene with Hypertension in Two Han Populations from Southern China

Hypertension is the most common and lethal risk factor for cardiovascular disease (CVD). Numerous variants have been associated with hypertension, however, most of which failed to get replication due to ethnic differences. In this study, we analyzed associations of 10 newly reported single nucleotide polymorphisms (SNPs) in Europeans with hypertension in Chinese. A total of 1766 samples consisting of 880 subjects with hypertension and 886 controls were collected and the SNPs were genotyped using multiple assays based on the SNaPshot mini-sequencing approach. Our results revealed a significant genotypic association of rs4746172 of VCL with hypertension with a lower frequency of minor allele in male subjects (OR = 0.70, 95% CI: 0.54-0.92, p = 0.011) but not in females. To validate the result, we genotyped the SNPs in another Chinese population with 546 individuals, and got a consistent association for the rs4746172 (OR = 0.56, 95% CI: 0.38-0.82, p = 2.4 × 10(-3)) in males. The VCL-encoding protein was involved in cardiomyopathy that associated with hypertension, therefore our results suggest the rs4746172 of VCL may be a novel target for clinical interventions to reduce CVD risk by regulating blood pressure in male Chinese.