The Association of C-Reactive Protein and CRP Genotype with Coronary Heart Disease: Findings from Five Studies with 4,610 Cases amongst 18,637 Participants
The Association of C-Reactive Protein and CRP Genotype with Coronary Heart Disease: Findings from Five Studies with 4,610 Cases amongst 18,637 Participants
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DOI：
10.1371/journal.pone.0003011
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发表时间：
2008-08-20
期刊：
影响因子：
3.7
通讯作者：
Smith, George Davey
中科院分区：
文献类型：
--
作者：
Lawlor, Debbie A.;Harbord, Roger M.;Smith, George Davey
背景：目前尚不清楚C反应蛋白（CRP）是否与冠心病（CHD）有因果关系。已知与CRP水平相关的遗传变异可用于提供CRP对CHD影响的因果推断。我们的目的是研究CRP基因变异+1444C>T与（rs 1130864）和冠心病风险的最大研究，迄今为止，这种关联。我们估计了CRP基因变异+1444C>T（rs 1130864）与CRP水平和CHD在5项研究中，然后汇总这些分析（N= 18，637名参与者，其中有4，610例病例）。CRP与潜在的混杂因素（社会经济地位、体力活动、吸烟和体重）相关，而基因型（rs 1130864）与这些混杂因素无关。校正年龄和性别后，循环CRP水平每增加一倍发生CHD的合并比值比为1.13（95% CI：1.06，1.21），进一步校正混杂因素后为1.07（95% CI：1.02，1.13）。基因型（rs 1130864）与循环CRP相关; TT基因型个体与CT/CC基因型个体之间CRP水平几何平均值的合并比值为1.21（95% CI：1.15，1.28），每个额外T等位基因的CRP水平几何平均值的合并比值为1.14（95% CI：1.11，1.18），两项分析中均无研究间异质性的强有力证据（两项分析的I-2 = 0%，p>0.9）。基因型（rs 1130864）与CHD无关联：TT基因型个体与CT/CC基因型个体的合并比值比为1.01（95%CI：0.88，1.16），每增加一个T等位基因（I-2），合并比值比为0.96（95%CI：0.90，1.03
Background: It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.Methods and Results: We estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N= 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95% CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95% CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95% CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95% CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I-2 = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95% CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95% CI: 0.90, 1.03) per additional T allele (I-2