title: Alcohol consumption, genetic variants in alcohol deydrogenases, and risk of cardiovascular diseases: a prospective study and meta-analysis.
abstract: OBJECTIVE
  First, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk.
  
  
  METHODS
  We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.2±2.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011.
  
  
  RESULTS
  Compared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10-0.97) and among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33-0.98) or >60 g alcohol/d (HR = 0.30; 95% CI: 0.12-0.78). Stroke risk was not significantly related to alcohol consumption >6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slow-coding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98-1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90-1.27; p for heterogeneity: 0.098)].
  
  
  CONCLUSIONS
  The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. drogan@dife.de
authors.forename: Dagmar
authors.initials: D
authors.lastname: Drogan
authors.forename: Abigail J
authors.initials: AJ
authors.lastname: Sheldrick
authors.forename: Madlen
authors.initials: M
authors.lastname: Schütze
authors.forename: Sven
authors.initials: S
authors.lastname: Knüppel
authors.forename: Frank
authors.initials: F
authors.lastname: Andersohn
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.forename: Bianca
authors.initials: B
authors.lastname: Herrmann
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Willich
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
authors.forename: Manuela M
authors.initials: MM
authors.lastname: Bergmann
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase