Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China
Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China
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DOI：
10.1016/s0140-6736(18)31772-0
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发表时间：
2019-05-04
期刊：
影响因子：
168.9
通讯作者：
Chen, Zhengming
中科院分区：
文献类型：
--
作者：
Millwood, Iona Y.;Walters, Robin G.;Chen, Zhengming
背景：许多研究表明，与戒酒或酗酒相比，适量饮酒与心血管风险降低有关。东亚的研究可以帮助确定这些关联是否是因果关系，因为两种常见的遗传变异极大地影响了饮酒模式。我们使用这两个变量来评估男性心血管风险与基因型预测的平均酒精摄入量之间的关系，并将男性的发现与女性（其中很少有人喝酒）的发现进行比较。方法前瞻性中国嘉道理生物库于2004年6月25日至2008年7月15日期间招募了来自中国十个地区的512 715名成年人，记录酒精使用情况和其他特征。它跟踪了他们大约10年（直到2017年1月1日），通过与发病率和死亡率登记和电子医院记录的联系监测心血管疾病（包括缺血性卒中，脑出血和心肌梗死）。研究人员对161498名参与者进行了两种改变酒精代谢的变体ALDH 2-rs671和ADH 1B-rs 1229984的基因分型。校正后的考克斯回归用于获得疾病发病率与自我报告的饮酒模式相关的相对风险（传统流行病学）或基因型预测的平均男性酒精摄入量（遗传流行病学-即孟德尔随机化），根据研究区域进行分层，以控制疾病发生率和基因型预测摄入量区域之间的差异。据报告，210 205名男性中有69 897人在大多数星期内饮酒，主要是烈酒，而女性中只有2%（6 245/302 510）。在男性中，传统流行病学显示，自我报告的酒精摄入量与缺血性中风（n=14930），脑出血（n=3496）和急性心肌梗死（n=2958）的发病率呈U形相关;每周饮酒约100 g（每天1至2杯）的男性比不饮酒者或重度饮酒者患所有三种疾病的风险更低。相比之下，尽管基因型预测的平均男性酒精摄入量变化很大（从每周4克到256克，即每天接近零到大约四杯），但它与风险没有任何U形关联。对于卒中，基因型预测的平均酒精摄入量与风险呈持续正对数线性相关，这在脑出血中更强（相对风险[RR]/280 g/周1.58，95%CI 1.36-1.84，p
Background Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink).Methods The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake.Findings 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1.58, 95% CI 1.36-1.84, p