Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach.
Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach.
复制标题
酒精摄入和血压：实施孟德尔随机方法的系统评价。
DOI：
10.1371/journal.pmed.0050052
复制
发表时间：
2008-03-04
期刊：
影响因子：
15.8
通讯作者：
Lewis SJ
中科院分区：
文献类型：
--
作者：
Chen L;Smith GD;Harbord RM;Lewis SJ
据报道，酒精是高血压的一个常见且可改变的危险因素。然而，观察性研究容易受到其他行为和社会人口因素的干扰，而临床试验难以实施，随访时间有限。孟德尔随机化可以通过使用醛脱氢酶2 （ALDH2）的常见多态性作为测量酒精摄入量的替代方法，为这种关联的本质提供强有力的证据。ALDH2编码一种参与酒精代谢的主要酶。与野生型纯合子（*1*1）或杂合子相比，纯合子（*2*2）的个体在饮酒时会出现不良症状。我们假设这种多态性可能通过影响饮酒行为来影响高血压的风险。我们对ALDH2基因型与血压（5项研究，n = 7658）和高血压（3项研究，n = 4219）进行了固定效应荟萃分析，这些研究通过系统评价确定。在男性中，我们获得了*1*1与*2*2纯合子比较高血压的总比值比为2.42(95%可信区间[CI] 1.66-3.55, p = 4.8 × 10−6)，杂合子（中度饮酒者的替代）与*2*2纯合子比较的总比值比为1.72 （95% CI 1.17-2.52, p = 0.006）。*1*1合子的收缩压比*2*2纯合子高7.44 mmHg (95% CI 5.39 ~ 9.49, p = 1.1 × 10−12)，杂合子的收缩压比*2*2纯合子高4.24 mmHg （95% CI 2.18 ~ 6.31, p = 0.00005）。这些发现支持了酒精摄入对血压和高血压风险有显著影响的假设。使用孟德尔随机化方法，Sarah Lewis和同事发现酒精摄入对血压和高血压风险有显著影响的假设得到了强有力的支持。高血压是一种常见的疾病，影响着近三分之一的美国和英国成年人。高血压没有症状，但可导致心脏病发作或中风。它是通过测量血压来诊断的——血压是指血液在体内流动时对大血管内部施加的力。当心脏泵出血液时血压最高（收缩压），当心脏充满血液时血压最低（舒张压）。正常血压的定义是收缩压小于130毫米汞柱（mmHg），舒张压小于85毫米汞柱（血压130/85）。读数超过140/90表明有高血压。影响血压的因素很多，但超重的人和吃太多咸或高脂肪食物的人患高血压的风险很高。轻度高血压通常可以通过改变生活方式来纠正，但许多人也服用降压药来降低血压。另一个被认为影响血压的可改变的生活方式因素是酒精摄入量。观察性研究询问了人们的饮酒习惯并测量了他们的血压，结果表明酒精摄入量与血压有关，但由于“混杂”——与饮酒有关的其他风险因素，如饮食，也可能影响研究参与者的血压，因此不能证明两者之间存在因果关系。一项随机分配不同酒精摄入量的试验可以提供这种因果关系的证据，但这样的试验是不切实际的。因此，在这项研究中，研究人员使用“孟德尔随机化”来调查饮酒是否会影响血压。一种醛脱氢酶2 （ALDH2；从体内去除酒精的酶）的无活性变体已被确定。从父母双方遗传这种基因变体的人有ALDH2 *2*2基因型（基因组成），喝酒后会脸红和恶心。因此，他们比*1*2基因型的人喝得少，比*1*1基因型的人喝得少得多。由于这些基因变异的遗传不影响除酒精摄入量以外的生活方式因素，因此ALDH2基因型与血压之间的关联表明，酒精摄入量对血压有影响，没有任何混淆。研究人员确定了10项已发表的研究（主要是在ALDH2基因变异很常见的日本进行的），这些研究使用了详细的搜索方案（“系统回顾”）来研究ALDH2基因型与血压或高血压之间的关系。对调查ALDH2基因型与高血压相关性的研究进行荟萃分析（结合独立研究结果的统计方法）显示，*1*1基因型（最高酒精摄入量）和*1*2基因型（中等酒精摄入量）男性患高血压的可能性分别是*2*2基因型（最低酒精摄入量）男性的2.42倍和1.72倍。在这些研究中，ALDH2基因型与高血压之间没有关联，因为她们饮酒很少。在第二项相关研究的荟萃分析中，收缩压和舒张压与ALDH2基因型的关系相似。最后，研究人员估计，对于男性来说，每天饮用1克酒精（一单位酒精在英国含有8克酒精，在美国含有14克酒精；这些国家的推荐每日限量分别为3-4和1 - 2单位）的终生影响将是收缩压增加0.24毫米汞柱。这些发现支持了酒精对血压和高血压有显著影响的说法。因此，一些高血压病例可以通过鼓励人们减少每天的酒精摄入量来预防。尽管孟德尔随机化方法避免了观察性研究固有的大多数混淆，但ALDH2附近的基因可能对酒精摄入量没有影响，因为基因通常是成块遗传的。另外，ALDH2可以独立于酒精摄入影响血压。ALDH2独立于酒精摄入影响血压的可能性不大，因为在饮酒量很少的女性中没有发现基因型对血压的影响。需要更多的大规模研究来解决这些可能性，在更多人身上证实目前的发现，并改进对酒精摄入对血压影响的估计。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0050052访问这些网站。MedlinePlus百科全书有一个关于高血压的页面（英语和西班牙语）美国心脏协会为患者和健康专业人员提供有关高血压的信息英国血压协会为患者和健康专业人员提供有关高血压的各个方面的信息。包括酒精影响血压的信息Explore@Bristol科学中心（一个英国慈善机构）提供了一个酒精单位计算器和关于酒精影响的信息，国际酒精政策中心为世界各国提供了饮酒指南
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour. We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes. These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension. Using a mendelian randomization approach Sarah Lewis and colleagues find strong support for the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension. High blood pressure (hypertension) is a common medical condition that affects nearly a third of US and UK adults. Hypertension has no symptoms but can lead to heart attacks or strokes. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic pressure) and lowest when it is filling up with blood (diastolic pressure). Normal blood pressure is defined as a systolic pressure of less than 130 millimeters of mercury (mmHg) and a diastolic pressure of less than 85 mmHg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat too much salty or fatty foods are at high risk of developing hypertension. Mild hypertension can often be corrected by lifestyle changes, but many people also take antihypertensive drugs to reduce their blood pressure. Another modifiable lifestyle factor thought to affect blood pressure is alcohol intake. Observational studies that ask people about their drinking habits and measure their blood pressure suggest that alcohol intake correlates with blood pressure, but they cannot prove a causal link because of “confounding”—other risk factors associated with alcohol drinking, such as diet, might also affect the study participant's blood pressures. A trial that randomly assigns people to different alcohol intakes could provide this proof of causality, but such a trial is impractical. In this study, therefore, the researchers have used “Mendelian randomization” to investigate whether alcohol intake affects blood pressure. An inactive variant of aldehyde dehydrogenase 2 (ALDH2; the enzyme that removes alcohol from the body) has been identified. People who inherit the variant form of this gene from both parents have an ALDH2 *2*2 genotype (genetic makeup) and become flushed and nauseated after drinking. Consequently, they drink less than people with a *1*2 genotype and much less than those with a *1*1 genotype. Because inheritance of these genetic variants does not affect lifestyle factors other than alcohol intake, an association between ALDH2 genotypes and blood pressure would indicate that alcohol intake has an effect on blood pressure without any confounding. The researchers identified ten published studies (mainly done in Japan where the ALDH2 gene variant is common) on associations between ALDH2 genotype and blood pressure or hypertension using a detailed search protocol (a “systematic review”). A meta-analysis (a statistical method for combining the results of independent studies) of the studies that had investigated the association between ALDH2 genotype and hypertension showed that men with the *1*1 genotype (highest alcohol intake) and those with the *1*2 genotype (intermediate alcohol intake) were 2.42 and 1.72 times more likely, respectively, to have hypertension than those with the *2*2 genotype (lowest alcohol intake). There was no association between ALDH2 genotype and hypertension among the women in these studies because they drank very little. Systolic and diastolic blood pressures showed a similar relationship to ALDH2 genotype in a second meta-analysis of relevant studies. Finally, the researchers estimated that for men the lifetime effect of drinking 1 g of alcohol a day (one unit of alcohol contains 8 g of alcohol in the UK and 14 g in the US; recommended daily limits in these countries are 3–4 and 1–2 units, respectively) would be an increase in systolic blood pressure of 0.24 mmHg. These findings support the suggestion that alcohol has a marked effect on blood pressure and hypertension. Consequently, some cases of hypertension could be prevented by encouraging people to reduce their daily alcohol intake. Although the Mendelian randomization approach avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks. Alternatively, ALDH2 could affect blood pressure independent of alcohol intake. The possibility that ALDH2 could effect blood pressure independently of alcohol is intake made unlikely by the fact that no effect of genotype on blood pressure is seen among women who drink very little. Additional large-scale studies are needed to address these possibilities, to confirm the current finding in more people, and to improve the estimates of the effect that alcohol intake has on blood pressure. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050052. The MedlinePlus encyclopedia has a page on hypertension (in English and Spanish) The American Heart Association provides information for patients and health professionals about hypertension The UK Blood Pressure Association provides information for patients and health professionals on all aspects of hypertension, including information about alcohol affects blood pressure The Explore@Bristol science center (a UK charity) provides an alcohol unit calculator and information on the effects of alcohol The International Center for Alcohol Policies provides drinking guidelines for countries around the world
登录
查看更多内容
影响因子：
3.2
作者：
TSURITANI, I;IKAI, E;YAMADA, Y
通讯作者：
YAMADA, Y
影响因子：
4.9
作者：
Saito, K;Yokoyama, J;Tanaka, H
通讯作者：
Tanaka, H
影响因子：
13.5
作者：
BOSRON, WF;LI, TK
通讯作者：
LI, TK
影响因子：
3.8
作者：
Lewis, SJ;Smith, GD
通讯作者：
Smith, GD
影响因子：
3.2
作者：
Lukasiewicz, E;Mennen, LI;Hercberg, S
通讯作者：
Hercberg, S