Grammer Tanja B, März Winfried, Renner Wilfried, Böhm Bernhard O, Hoffmann Michael M
Synlab Centre of Laboratory Diagnostics Heidelberg, PO Box 10 47 80, D-69037 Heidelberg, Germany.
Eur Heart J. 2009 Jan;30(2):170-82. doi: 10.1093/eurheartj/ehn191. Epub 2008 May 21.
Circulating C-reactive protein is associated with future cardiovascular events. The causal role of C-reactive protein in the development of atherosclerosis remains controversial.
We analysed the association between three genetic polymorphisms (PM) (-717C>T, rs2794521; +1059G>C, rs1800947; +1444C>T, rs1130864) at the C-reactive protein locus and related haplotypes with both circulating C-reactive protein and angiographic coronary artery disease (CAD). The concentration of C-reactive protein was similar in patients with stable CAD and in controls, but increased in patients presenting with acute coronary syndromes. In models adjusting for the main confounding variables, the minor alleles of the +1059G>C (rs1800947) and the +1444C>T PM (rs1130864) were associated with decreased and increased concentrations of C-reactive protein, respectively. Haplotypes 1 and 4 decreased, and haplotype 2 increased C-reactive protein, whereas haplotype 3 had no appreciable effect. None of the genetic variants affecting circulating C-reactive protein was consistently associated with the prevalence of angiographic CAD.
A causal role of C-reactive protein in the development of CAD would require that genetic PM resulting in long-term modulation of the concentration of C-reactive protein be themselves associated with CAD. We were not able to detect such a relationship, which can be attributed to either a very small genetic effect size or the relationship between C-reactive protein and cardiovascular events may reflect confounding and reverse causation.
循环C反应蛋白与未来心血管事件相关。C反应蛋白在动脉粥样硬化发展中的因果作用仍存在争议。
我们分析了C反应蛋白基因座上的三种基因多态性（PM）（-717C>T，rs2794521；+1059G>C，rs1800947；+1444C>T，rs1130864）及相关单倍型与循环C反应蛋白和血管造影冠状动脉疾病（CAD）之间的关联。稳定型CAD患者和对照组的C反应蛋白浓度相似，但急性冠状动脉综合征患者的C反应蛋白浓度升高。在对主要混杂变量进行校正的模型中，+1059G>C（rs1800947）的次要等位基因和+1444C>T PM（rs1130864）分别与C反应蛋白浓度降低和升高相关。单倍型1和4使C反应蛋白降低，单倍型2使C反应蛋白升高，而单倍型3没有明显影响。影响循环C反应蛋白的基因变异均与血管造影CAD的患病率无一致关联。
C反应蛋白在CAD发展中的因果作用需要导致C反应蛋白浓度长期调节的基因多态性本身与CAD相关。我们未能检测到这种关系，这可能归因于基因效应大小非常小，或者C反应蛋白与心血管事件之间的关系可能反映了混杂和反向因果关系。
