Kardys Isabella, Klaver Caroline C W, Despriet Dominiek D G, Bergen Arthur A B, Uitterlinden André G, Hofman Albert, Oostra Ben A, Van Duijn Cornelia M, de Jong Paulus T V M, Witteman Jacqueline C M
Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
J Am Coll Cardiol. 2006 Apr 18;47(8):1568-75. doi: 10.1016/j.jacc.2005.11.076. Epub 2006 Mar 29.
This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease.
The evidence that inflammation is an important mechanism in atherogenesis is growing. C-reactive protein (CRP), complement factors, and complement regulatory factors have all been linked to coronary heart disease. The CFH gene is an important regulator of the alternative complement cascade. We investigated its association with coronary heart disease.
The study was embedded in the Rotterdam Study, a prospective population-based study among men and women aged 55 years and over. A total of 5,520 participants without history of coronary heart disease was genotyped for the Tyr402His polymorphism of the CFH gene. Cox proportional hazards analysis was used to determine risk of myocardial infarction for Tyr402His genotypes.
Mean age among participants was 69.5 years (SD 9.1 years). The overall frequency of the His allele was 36%; genotype frequencies were 41%, 45%, and 14% for TyrTyr, TyrHis, and HisHis, respectively. During a mean follow-up period of 8.4 years, 226 myocardial infarctions occurred. After adjustment for age, gender, established cardiovascular risk factors, and CRP level, HisHis homozygotes had a hazard ratio of 1.77 (95% confidence interval 1.23 to 2.55) for myocardial infarction. Total cholesterol level, diabetes mellitus, and smoking modified the effect. The Tyr402His polymorphism was not associated with established cardiovascular risk factors or CRP level.
Our data suggest that the CFH gene determines susceptibility to myocardial infarction. This finding underscores the importance of the alternative complement system in cardiovascular disease.
本研究旨在调查补体因子H（CFH）基因中的常见多态性（Tyr402His，rs1061170）与冠心病风险之间的关联。
炎症是动脉粥样硬化发生的重要机制这一证据日益增多。C反应蛋白（CRP）、补体因子和补体调节因子均与冠心病有关。CFH基因是替代补体级联反应的重要调节因子。我们调查了其与冠心病的关联。
该研究纳入鹿特丹研究，这是一项针对55岁及以上男性和女性的基于人群的前瞻性研究。对5520名无冠心病病史的参与者进行CFH基因Tyr402His多态性的基因分型。采用Cox比例风险分析来确定Tyr402His基因型发生心肌梗死的风险。
参与者的平均年龄为69.5岁（标准差9.1岁）。His等位基因的总体频率为36%；TyrTyr、TyrHis和HisHis基因型频率分别为41%、45%和14%。在平均8.4年的随访期内，发生了226例心肌梗死。在调整年龄、性别、已确定的心血管危险因素和CRP水平后，HisHis纯合子发生心肌梗死的风险比为1.77（95%置信区间1.23至2.55）。总胆固醇水平、糖尿病和吸烟会改变这种效应。Tyr402His多态性与已确定的心血管危险因素或CRP水平无关。
我们的数据表明CFH基因决定了对心肌梗死的易感性。这一发现强调了替代补体系统在心血管疾病中的重要性。
