Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans

Abstract

Objectives: Recent genome-wide association studies have identified a number of variants influencing blood pressure. We aimed to examine whether these associations can be replicated in Chinese.

Methods: We genotyped eight of these variants (in or near FGF5, CYP17A1, MTHFR, ZNF652, PLCD3, ATP2B1, c10orf107) in a population-based cohort of Chinese Hans (N = 3210). Logistics regression and generalized linear analyses were applied to test for association of each variant with hypertension risk and blood pressure (BP), BMI, waistline and high-sensitivity C-reactive protein (hsCRP), respectively.

Results: Six variants showed directionally consistent association with blood pressure and risk of hypertension, of which four (FGF5, two in CYP17A1, MTHFR) reached significance. The associations were most pronounced for FGF5-rs16998073 [SBP: β = 1.97 mmHg/allele, P = 0.0006; DBP: β = 0.95 mmHg/allele, P = 0.0008, hypertension: odds ratio (OR) 1.36/allele, P = 0.0001]. Effect size of FGF5-rs16998073 on SBP and hypertension were significantly more pronounced in Han Chinese compared to white Europeans. None of these variants was associated with BMI, waistline or hsCRP that are the well established risk factors for hypertension. The genetic risk score, calculated as the sum of BP-increasing alleles of FGF5-rs16998073, CYP17A1-rs11191548, CYP17A1-rs1004467 and MTHFR-rs17367504, was significantly associated with increased SBP (1.16 mmHg/allele, P = 9.01E-5), DBP (0.51 mmHg/allele, P = 4.40E-4) and hypertension risk (OR = 1.22/allele, P = 2.74E-7).

Conclusion: Variants in or near FGF5, CYP17A1 and MTHFR contributed to variation in BP and hypertension risk. Effect sizes of these three loci tended to be larger in Chinese than in white Europeans, but more studies with larger sample size are required for a definitive conclusion.