Genetic risk assessment for cardiovascular disease with seven genes associated with plasma C-reactive protein concentrations in Asian populations

Plasma C-reactive protein (CRP) level is a predictor of cardiovascular risk. We performed a meta-analysis on the effect of 12 single-nucleotide polymorphisms (SNPs) within 8 candidate loci in 36 752 Asians. In addition, we created weighted genetic risk scores (wGRSs) to evaluate the combined effects of genetic variants, which were suggested in the meta-analysis, for predicting the risks of elevated CRP levels as well as increased risks of hypertension and cardiovascular disease (CVD) in 748 Koreans. Nine SNPs located in seven genes, CRP , IL6R , GCKR , IL6 , CYP17A1 , HNF1A and APOE , were significantly associated with circulating CRP levels in this meta-analysis. Two SNPs, rs7310409 ( HNF1A , P =3.4 × 10 −23 ) and rs7553007 ( CRP , P =3.4 × 10 −17 ), had the most significant effects on CRP levels; and two SNPs, rs2097677 ( IL6 ) and rs1004467 ( CYP17A1 ) have never been found in the previous European meta-analysis. In Koreans, the subjects in the highest wGRS group had an ∼2.5-fold higher mean CRP level compared with those in the lowest wGRS group ( P =2.1 × 10 −5 ). We observed significant increases in the risks of hypertension (odds ratio=2.18, P =0.006) and CVD (odds ratio=9.59, P =3.2 × 10 −6 ) among the subjects in the highest wGRS group. The wGRS models specific to Koreans may warrant further validation to be used as a proxy for the risk of CVD in Asians.