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Holmes, Michael V; Dale, Caroline E; Zuccolo, Luisa; Silverwood, Richard J; Guo, Yiran; Ye, Zheng; Prieto-Merino, David; Dehghan, Abbas; Trompet, Stella; Wong, Andrew; Cavadino, Alana; Drogan, Dagmar; Padmanabhan, Sandosh; Li, Shanshan; Yesupriya, Ajay; Leusink, Maarten; Sundstrom, Johan; Hubacek, Jaroslav A; Pikhart, Hynek; Swerdlow, Daniel I; Panayiotou, Andrie G; Borinskaya, Svetlana A; Finan, Chris; Shah, Sonia; Kuchenbaecker, Karoline B; Shah, Tina; Engmann, Jorgen; Folkersen, Lasse; Eriksson, Per; Ricceri, Fulvio ... view all 155 authors View less authors (2014)
Publisher: BMJ Publishing Group Ltd.
Journal: The BMJ
Languages: English
Types: Article
Subjects: Kardiologi, Models, Statistical, RISK-FACTORS, Alcohol Dehydrogenase, VARIANTS, Mendelian Randomization Analysis, DEHYDROGENASE, Research, Coronary Disease, 616.1 [udc], DESIGN, Polymorphism, Single Nucleotide, CORONARY-HEART-DISEASE, DEPENDENCE, Cardiac and Cardiovascular Systems, Female, Alcohol drinking ; Adverse effects ; Alcoholism ; Epidemiology ; Cardiovascular diseases ; Epidemiology ; Regression analysis ; Meta-analysis as topic, METAANALYSIS, Aged, HEALTH, CONSUMPTION, Middle Aged, Stroke, Alcohol Drinking, Genotype, MORTALITY, Biological Markers, Adult; Aged; Alcohol Dehydrogenase/genetics; Alcohol Drinking/adverse effects; Alcohol Drinking/genetics; Biomarkers/blood; Coronary Disease/blood; Coronary Disease/etiology; Coronary Disease/genetics; Female; Genetic Markers; Genotype; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Models, Statistical; Polymorphism, Single Nucleotide; Stroke/blood; Stroke/etiology; Stroke/genetics, Adult, Genetic Markers, Humans, Male
Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.

\ud \ud Design: Mendelian randomisation meta-analysis of 56 epidemiological studies.

\ud \ud Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.

\ud \ud Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.

\ud \ud Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).

\ud \ud Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

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