Hawe E, Talmud P J, Miller G J, Humphries S E
Centre for Cardiovascular Genetics, Dept Medicine, Royal Free and University College London Medical School, Rayne Institute, UK.
Ann Hum Genet. 2003 Mar;67(Pt 2):97-106. doi: 10.1046/j.1469-1809.2003.00017.x.
We have estimated the risk of coronary heart disease (CHD) from family history of CHD (FHCHD) in 2827 healthy European middle-aged men, and explored the extent to which this can be explained by classical and genetic risk factors. Men with FHCHD (obtained by questionnaire) had a hazard ratio of CHD of 1.73 (95% confidence interval: 1.30, 2.31) compared to those without FHCHD; after adjusting for classical risk factors this did not change substantially. Those with FHCHD had 2.3% lower Factor VIIc (p = 0.03) and 1.14% higher systolic and 1.21% higher diastolic blood pressure (p = 0.04 and p = 0.02), with evidence of interaction between blood pressure and FHCHD status on risk (p = 0.01). The risk for those with a positive family history who were also current smokers was 3.01 compared to non-smokers without FHCHD, which is greater than the risk posed by smoking or FHCHD alone (1.96 and 2.05 respectively compared to non-smokers without FHCHD), but not significantly different from a multiplicative model (p-value for interaction 0.33). Allele frequencies for 13 candidate gene variants were not significantly different between those with and without FHCHD. In those with FHCHD, current smokers who carried the APOE4 allele (e4+) had a hazard ratio of 5.66 compared to non-smokers who had no FHCHD and were not APOE4+, with a significant interaction between smoking and APOE4 in those with FHCHD p = 0.001. These data demonstrate the complex interaction between genetic and environmental factors in determining CHD risk, and suggest that the causes of the familial clustering of CHD remain largely unexplained.
我们在2827名健康的欧洲中年男性中，根据冠心病家族史（FHCHD）估算了冠心病（CHD）风险，并探究了经典风险因素和遗传风险因素在多大程度上能够解释这种风险。与无FHCHD者相比，有FHCHD（通过问卷获得）的男性患CHD的风险比为1.73（95%置信区间：1.30, 2.31）；在调整经典风险因素后，这一数值变化不大。有FHCHD者的凝血因子VIIc降低2.3%（p = 0.03），收缩压升高1.14%，舒张压升高1.21%（p = 0.04和p = 0.02），且血压与FHCHD状态在风险上存在相互作用的证据（p = 0.01）。与无FHCHD的非吸烟者相比，有家族史且当前吸烟的人群的风险为3.01，这高于单独吸烟或FHCHD所带来的风险（与无FHCHD的非吸烟者相比，分别为1.96和2.05），但与相乘模型无显著差异（相互作用的p值为0.33）。13种候选基因变异的等位基因频率在有FHCHD者和无FHCHD者之间无显著差异。在有FHCHD者中，携带APOE4等位基因（e4+）的当前吸烟者与无FHCHD且非APOE4+的非吸烟者相比，风险比为5.66，在有FHCHD者中吸烟与APOE4之间存在显著相互作用（p = 0.001）。这些数据表明，在确定CHD风险方面，遗传和环境因素之间存在复杂的相互作用，并表明CHD家族聚集性的原因在很大程度上仍未得到解释。
