Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data.
Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data.
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DOI：
10.1136/bmj.d548
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Danesh J
中科院分区：
文献类型：
--
作者：
C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC);Wensley F;Gao P;Burgess S;Kaptoge S;Di Angelantonio E;Shah T;Engert JC;Clarke R;Davey-Smith G;Nordestgaard BG;Saleheen D;Samani NJ;Sandhu M;Anand S;Pepys MB;Smeeth L;Whittaker J;Casas JP;Thompson SG;Hingorani AD;Danesh J
目的应用遗传变异作为C反应蛋白浓度的无混杂代表，研究其在冠心病发病中的作用。设计孟德尔随机化荟萃分析的个人参与者的数据来自47个流行病学研究在15个国家。研究对象194418名受试者，包括46557名冠心病患者。可获得关于4种CRP基因标记单核苷酸多态性（rs3093077、rs 1205、rs 1130864、rs 1800947）、C反应蛋白浓度和其他危险因素水平的信息。主要结果测量与遗传性C反应蛋白升高相关的冠心病风险比与C反应蛋白浓度本身具有同等差异的风险比，调整了常规风险因素和个体内风险因素水平的变异性。结果CRP变异体与C反应蛋白浓度的等位基因差异高达30%相关（P<10 - 34），与其他危险因素无关。与C反应蛋白升高相关的等位基因每增加一个拷贝，冠心病的风险比为0.93 rs3093077的（95%置信区间0.87 - 1.00）; 1.00（0.98至1.02）; rs 1130864为0.98（0.96至1.00）; rs 1800947为0.99（0.94至1.03）。在综合分析中，冠心病的风险比为1.00（0.90至1.13）每1 SD的遗传提高自然对数（ln）浓度的C反应蛋白。在前瞻性研究中，观察到的冠心病风险比为1.33（1.23至1.43）/1 SD，循环ln C反应蛋白浓度升高（差异P=0.001），遗传学结果与此不一致。结论人类遗传学数据表明，C反应蛋白浓度本身不太可能是冠心病的一个温和的致病因素。
Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P<10−34) and were unrelated to other risk factors. Risk ratios for coronary heart disease per additional copy of an allele associated with raised C reactive protein were 0.93 (95% confidence interval 0.87 to 1.00) for rs3093077; 1.00 (0.98 to 1.02) for rs1205; 0.98 (0.96 to 1.00) for rs1130864; and 0.99 (0.94 to 1.03) for rs1800947. In a combined analysis, the risk ratio for coronary heart disease was 1.00 (0.90 to 1.13) per 1 SD higher genetically raised natural log (ln) concentration of C reactive protein. The genetic findings were discordant with the risk ratio observed for coronary heart disease of 1.33 (1.23 to 1.43) per 1 SD higher circulating ln concentration of C reactive protein in prospective studies (P=0.001 for difference). Conclusion Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.
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影响因子：
37.8
作者：
Koike T;Kitajima S;Yu Y;Nishijima K;Zhang J;Ozaki Y;Morimoto M;Watanabe T;Bhakdi S;Asada Y;Chen YE;Fan J
通讯作者：
Fan J
影响因子：
2.5
作者：
Crossman, David C.;Morton, Allison C.;Gunn, Julian P.;Greenwood, John P.;Hall, Alistair S.;Fox, Keith Aa;Lucking, Andrew J.;Flather, Marcus D.;Lees, Belinda;Foley, Claire E.
通讯作者：
Foley, Claire E.
DOI：
10.1073/pnas.0706027104
发表时间：
2007-08-21
影响因子：
11.1
作者：
Kovacs, Alexander;Tornvall, Per;Bjorkegren, Johan
通讯作者：
Bjorkegren, Johan
影响因子：
3.7
作者：
Lawlor, Debbie A.;Harbord, Roger M.;Smith, George Davey
通讯作者：
Smith, George Davey
影响因子：
37.8
作者：
Pearson, TA;Mensah, GA;Vinicor, F
通讯作者：
Vinicor, F