Institute of Biomedical Technologies/CNR, Italian National Research Council, Milan, Italy.
J Hum Hypertens. 2013 Aug;27(8):497-503. doi: 10.1038/jhh.2012.70. Epub 2013 Jan 17.
Data from a population-based prospective study were used to examine longitudinal changes in blood pressure (BP) and seek interactions between apolipoprotein E (ApoE) genotypes, smoking and alcohol in a cohort of 557 elderly Brazilian men. Repeated BP measurements were obtained in four waves, and multi-level random-effects pattern-mixture models were used to evaluate age-related BP trajectories while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. Alcohol was associated with high systolic BP in ε2 carriers and those with the ε3/3 genotype, but not in ε4 carriers. This was dependent on age and smoking habits: at the age of 60, expected systolic BP in alcohol drinking ε2 carriers was 16.5 mm Hg higher than in the reference group of non-smokers/non-drinkers if they were not smokers (P=0.049), and 28.6 mm Hg higher if they were also smokers (P=0.004). The youngest smoking/non-drinking ε2 carriers had lower systolic BP, but it increased rapidly and led to higher expected levels among older carriers. Alcohol consumption, alone or together with smoking, interacts with the effects of ApoE genotype on systolic BP, probably nullifying the more favourable lipid profile of ε2 carriers. The interactions of gene-modifiable risk factors have major public health implications.
利用基于人群的前瞻性研究数据,我们在一个由 557 名巴西老年男性组成的队列中,研究了血压(BP)的纵向变化,并探讨了载脂蛋白 E(ApoE)基因型、吸烟和饮酒之间的相互作用。在四个波次中获得了重复的 BP 测量值,并使用多级随机效应模式混合模型来评估与年龄相关的 BP 轨迹,同时考虑到不可忽略的失访/死亡以及处理异质性作为随机参数变化。酒精与 ε2 携带者和 ε3/3 基因型携带者的收缩压升高有关,但与 ε4 携带者无关。这取决于年龄和吸烟习惯:在 60 岁时,如果 ε2 携带者饮酒且不吸烟,他们的预期收缩压比不吸烟者/不饮酒者高 16.5mmHg(P=0.049),如果他们同时吸烟,则高 28.6mmHg(P=0.004)。最年轻的吸烟/不饮酒的 ε2 携带者的收缩压较低,但随着年龄的增长,收缩压迅速升高,导致较高的预期水平。饮酒,单独或与吸烟一起,与 ApoE 基因型对收缩压的影响相互作用,可能会抵消 ε2 携带者更有利的血脂谱。基因可修饰风险因素的相互作用具有重大的公共卫生意义。