title: Genetic risk assessment for cardiovascular disease with seven genes associated with plasma C-reactive protein concentrations in Asian populations.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Eun Pyo
authors.initials: EP
authors.lastname: Hong
authors.affiliation: 1] Department of Social and Preventive Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea [2] Hallym Research Institute of Clinical Epidemiology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Jun Gyo
authors.initials: JG
authors.lastname: Suh
authors.affiliation: Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Ji Wan
authors.initials: JW
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D055106:Genome-Wide Association Study; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001057:Apolipoproteins E; C485100:GCKR protein, human; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D015850:Interleukin-6; D002097:C-Reactive Protein; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase