Hong Eun Pyo, Kim Dong Hyun, Suh Jun Gyo, Park Ji Wan
Department of Medical Genetics, Hallym University College of Medicine, Chuncheon, Republic of Korea.
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.
Hypertens Res. 2014 Jul;37(7):692-8. doi: 10.1038/hr.2014.56. Epub 2014 Mar 27.
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.
血浆C反应蛋白（CRP）水平是心血管风险的一个预测指标。我们对36752名亚洲人8个候选基因座内的12个单核苷酸多态性（SNP）的影响进行了荟萃分析。此外，我们创建了加权遗传风险评分（wGRS）来评估遗传变异的综合效应，这些效应在荟萃分析中被提出，用于预测748名韩国人CRP水平升高的风险以及高血压和心血管疾病（CVD）风险的增加。在这项荟萃分析中，位于CRP、IL6R、GCKR、IL6、CYP17A1、HNF1A和APOE这7个基因中的9个SNP与循环CRP水平显著相关。两个SNP，rs7310409（HNF1A，P = 3.4×10⁻²³）和rs7553007（CRP，P = 3.4×10⁻¹⁷）对CRP水平的影响最为显著；还有两个SNP，rs2097677（IL6）和rs1004467（CYP17A1）在之前的欧洲荟萃分析中从未被发现。在韩国人中，wGRS最高组的受试者平均CRP水平比wGRS最低组的受试者高约2.5倍（P = 2.1×10⁻⁵）。我们观察到wGRS最高组的受试者中高血压风险（优势比 = 2.18，P = 0.006）和CVD风险（优势比 = 9.59，P = 3.2×10⁻⁶）显著增加。针对韩国人的wGRS模型可能需要进一步验证，以便用作亚洲人CVD风险的替代指标。
