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Meta-Analysis
. 2008 Mar 4;5(3):e52.
doi: 10.1371/journal.pmed.0050052.

Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach

Lina Chen  1 , George Davey Smith, Roger M Harbord, Sarah J Lewis
Affiliations
Meta-Analysis

Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach

Lina Chen et al. PLoS Med. .

Abstract

Background: 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.

Methods and findings: 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 x 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 x 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.

Conclusions: These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow Diagram Showing Reasons for Exclusion and Number of Papers Excluded
Figure 2
Figure 2. Forest Plot of Studies of ALDH2 Genotype and Hypertension
Figure 3
Figure 3. Forest Plot of Studies of ALDH2 Genotype and Blood Pressure
Figure 4
Figure 4. Mean Blood Pressure in Each Genotype Plotted against Mean Alcohol Consumption in Each Genotype in the Three Studies That Gave Data for Both Relationships
Top graph: systolic blood pressure. Bottom graph: diastolic blood pressure. Larger plotting symbols indicate a greater number of individuals.
Figure 5
Figure 5. Forest Plot of Instrumental Variable Estimates of Alcohol–Blood Pressure Effect in Males Obtained Using Genotype as an Instrument for Alcohol
See this image and copyright information in PMC

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