Confirmation of top polymorphisms in hypertension genome wide association study among Han Chinese

Abstract

Background: Confirmation of genome wide association (GWA) results in independent samples has recently become new research tendency. Methods: We focused on 8 positive top polymorphisms identified in the to-date largest hypertension GWA study and determined whether these polymorphisms were associated with hypertension among Han Chinese. Genotyping was performed among 548 patients diagnosed with essential hypertension and 560 age- and gender-matched controls using ligase detection reactions method. Statistical analyses were conducted using Logistic regression and genotype risk score. Results: Except for a rare polymorphism (rs653178), no deviation from Hardy-Weinberg equilibrium was observed for genotype distributions of others. There was significant differences in the genotype/allele distribution (P=0.006/P=0.002) of rs16998073 in FGF5 (fibroblast growth factor 5) upstream and the allele distribution (P=0.037) of rs16948048 in ZNF652 (zinc finger protein 652) upstream between hypertensive patients and controls. Strong significance was also noted under assumption of different genetic models for the two coalescent polymorphisms, even after controlling covariates of interest. For example, rs16998073 had a 72% increased risk for hypertension under the co-dominant model (95% confidence interval: 1.20-2.45; P=0.003). However, construction of genetic risk scores on common polymorphisms did not reveal any significance with both hypertension and blood pressure, suggesting that contribution of these polymorphisms to hypertension moderate or small in magnitude. Conclusions: Our results implicate variation in FGF5 and ZNF652 gene upstream regions with altered susceptibility to hypertension in Han Chinese. © 2010 Elsevier B.V.