State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hypertens Res. 2012 Oct;35(10):1019-23. doi: 10.1038/hr.2012.89. Epub 2012 Jul 5.
C-reactive protein (CRP), an acute phase reactant and marker of inflammation, has been shown to be associated with CRP genetic variants and incident hypertension, but it is unclear whether this link is causal. We therefore conducted a prospective, nested case-control study to examine the relationship between single-nucleotide polymorphisms (SNPs) within the CRP gene, circulating CRP levels and the development of hypertension. Plasma CRP levels and the genotypes of eight SNPs were determined in 2000 unrelated Shanghai residents, including 908 hypertensive individuals and 1092 normotensive individuals. Among the 1092 normotensives, 968 subjects were followed up for 2 years, during which 71 developed hypertension. Plasma CRP levels were independently associated with the development of hypertension in the follow-up study (odds ratio per quartile=1.64; 95% confidence interval: 1.18-2.26; P<0.001). The minor alleles of rs1130864 (P<0.001) and rs3093059 (P<0.001) were significantly associated with elevated CRP levels, and the minor alleles of rs1205, rs1800947 and rs2246469 (all P<0.001) were associated with decreased CRP levels. A haplotype-based analysis strengthened the results of single-locus analysis. However, none of the SNPs or haplotypes was significantly associated with blood pressure, incident hypertension or changes between baseline and follow-up blood pressure levels. Taken together, our findings demonstrated that plasma CRP levels were substantially associated with common genetic variants in the CRP gene and could predict the development of hypertension. However, the relationship between genotype and CRP levels was not associated with a change in hypertension risk.
C 反应蛋白（CRP）是一种急性期反应物和炎症标志物，已有研究表明其与 CRP 基因变异和高血压发病有关，但尚不清楚这种关联是否具有因果关系。因此，我们进行了一项前瞻性、巢式病例对照研究，以检验 CRP 基因内的单核苷酸多态性（SNP）、循环 CRP 水平与高血压发病之间的关系。在 2000 名无血缘关系的上海居民中，测定了 CRP 基因 8 个 SNP 的血浆 CRP 水平和基因型，包括 908 名高血压患者和 1092 名血压正常者。在 1092 名血压正常者中，有 968 名进行了 2 年的随访，其中 71 人发生了高血压。在随访研究中，血浆 CRP 水平与高血压发病独立相关（每四分位间距的比值比=1.64；95%置信区间：1.18-2.26；P<0.001）。rs1130864（P<0.001）和 rs3093059（P<0.001）的次要等位基因与 CRP 水平升高显著相关，rs1205、rs1800947 和 rs2246469 的次要等位基因与 CRP 水平降低显著相关（均 P<0.001）。基于单体型的分析加强了单基因座分析的结果。然而，没有一个 SNP 或单体型与血压、高血压发病或基线和随访血压水平之间的变化显著相关。综上所述，我们的研究结果表明，血浆 CRP 水平与 CRP 基因中的常见遗传变异密切相关，可预测高血压的发病。然而，基因型与 CRP 水平之间的关系与高血压发病风险的变化无关。
