Recapitulation of four hypertension susceptibility genes (CSK, CYP17A1, MTHFR, and FGF5) in East Asians

Objective: A recent genome wide association study identified eight hypertension susceptibility loci in Europeans. Subsequently, several studies have investigated these associations in East Asian populations. The results of these studies, however, have been inconsistent. A meta-analysis was performed to assess the associations of the most published polymorphisms, including CSK rs1378942, CYP17A1 rs11191548, MTHFR rs17367504, and FGF5 rs16998073 polymorphisms with hypertension.

Methods: Published literature from PubMed and Embase databases was retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model.

Results: Seven studies (16,368 cases /19,707 controls) for CSK rs1378942 polymorphism, seven studies (15,688 cases /18,784 controls) for CYP17A1 rs11191548 polymorphism, four studies (7994 cases / 12,844 controls) for MTHFR rs17367504 polymorphism, and three studies (6026 cases / 8393 controls) for FGF5 rs16998073 polymorphism were included in the meta-analysis. The results suggested that both CYP17A1 rs11191548 and FGF5 rs16998073 polymorphisms were significantly associated with hypertension risk in East Asians (CYP17A1 rs11191548 (random effect model): OR=1.16, 95% CI 1.07-1.25, p=3.59×10(-4), I(2)=78.2%, p (heterogeneity)=1.14×10(-4); FGF5 rs16998073 (random effect model): OR=1.30, 95% CI 1.23-1.37, p=6.29×10(-21), I(2)=65.0%, p (heterogeneity)=0.009); whereas no significant association was observed for CSK rs1378942 (fix effect model: OR=1.09, 95% CI 0.98-1.22, p=0.128, I(2)=0.0%, p (heterogeneity)=0.820), or MTHFR rs17367504 (fix effect model: OR=1.06, 95% CI 0.98-1.14, p=0.126, I(2)=0.0%, p (heterogeneity)=0.822).

Conclusion: The present meta-analysis indicated significant associations of both CYP17A1 rs11191548 and FGF5 rs16998073 polymorphisms with hypertension susceptibility in East Asians.