Stengård J H, Weiss K M, Sing C F
National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland.
Hum Genet. 1998 Aug;103(2):234-41. doi: 10.1007/s004390050811.
Three common alleles, epsilon2, epsilon3, and epsilon4, of the gene coding for apolipoprotein E (apoE) have been identified as predictors of interindividual variation in measures of lipid and lipoprotein metabolism, and ultimately risk of coronary heart disease (CHD), within many populations. Here we evaluated the utility of the geographic distribution of these alleles for prediction of interpopulation variation in average level of serum total cholesterol and other traditional risk factors, and CHD mortality rate. We employed published estimates of the relative frequencies of the three common apoE alleles, average levels of risk factors such as serum total cholesterol, systolic and diastolic blood pressure, body mass index, smoking prevalence and CHD mortality rate for nine population-based samples of middle-aged males studied by the international WHO MONICA Project. There was approximately a 10-fold difference between the highest and lowest CHD mortality rate. Of the traditional risk factors, variation in the average level of serum total cholesterol was the best predictor (approximately 33%) of the observed interpopulation variation in estimates of CHD mortality rate (Pr=0.10). Variation in the relative frequency of the epsilon4 allele predicted approximately 50% of interpopulation variation in average serum total cholesterol level (Pr=0.02) and 75% of the variation in CHD mortality rate (Pr=0.002) when information about variation in the other risk factors and the epsilon2 and epsilon3 alleles is ignored. Furthermore, variation in the relative frequency of the epsilon4 allele predicted approximately 40% of the variation in CHD mortality rate (Pr=0.02) after considering the contribution of variation in average serum total cholesterol level. Average serum total cholesterol level was estimated to increase by 0.114 mmol/l (4.405 mg/dl), and CHD mortality rate by 24.5/100000, for an increase of 0.01 in the relative frequency of the epsilon4 allele. The predictive utility of the epsilon2 and epsilon3 alleles was considerably less than that of the epsilon4 allele. For the sample of populations considered, the geographic distribution of the apoE alleles can be a statistically significant predictor of interpopulation variation in both the average serum total cholesterol level and CHD mortality rate. In particular, the epsilon4 allele may confer valuable ecological risk information.
编码载脂蛋白E（apoE）的基因有三种常见等位基因，即ε2、ε3和ε4，在许多人群中，它们已被确定为脂质和脂蛋白代谢指标个体间差异的预测因子，最终也是冠心病（CHD）风险的预测因子。在此，我们评估了这些等位基因的地理分布对于预测人群间血清总胆固醇平均水平及其他传统风险因子以及冠心病死亡率差异的效用。我们采用了已发表的关于三种常见apoE等位基因相对频率的估计值，以及世界卫生组织（WHO）国际MONICA项目研究的九个基于人群的中年男性样本的风险因子平均水平，如血清总胆固醇、收缩压和舒张压、体重指数、吸烟率及冠心病死亡率。冠心病死亡率最高值与最低值之间大约有10倍的差异。在传统风险因子中，血清总胆固醇平均水平的差异是观察到的人群间冠心病死亡率估计差异的最佳预测因子（约33%）（P = 0.10）。当忽略其他风险因子以及ε2和ε3等位基因的差异信息时，ε4等位基因相对频率的差异预测了约50%的人群间血清总胆固醇平均水平差异（P = 0.02）以及75%的冠心病死亡率差异（P = 0.002）。此外，在考虑血清总胆固醇平均水平差异的贡献后，ε4等位基因相对频率的差异预测了约40%的冠心病死亡率差异（P = 0.02）。ε4等位基因相对频率每增加0.01，估计血清总胆固醇平均水平会升高0.114 mmol/l（4.405 mg/dl），冠心病死亡率会升高24.5/100000。ε2和ε3等位基因的预测效用远低于ε4等位基因。对于所考虑的人群样本，apoE等位基因的地理分布在统计学上可显著预测人群间血清总胆固醇平均水平及冠心病死亡率的差异。特别是，ε4等位基因可能提供有价值的生态风险信息。
