TY - JOUR A1 - Drogan, D. A1 - Sheldrick, A. J. A1 - Schütze, M. A1 - Knüppel, S. A1 - Andersohn, F. A1 - di Giuseppe, R. A1 - Herrmann, Bianca A1 - Willich, S. N. A1 - Garbe, E. A1 - Bergmann, M. M. A1 - Boeing, H. A1 - Weikert, C. T1 - Alcohol consumption, genetic variants in alcohol deydrogenases, and risk of cardiovascular diseases: A prospective study and meta-analysis N2 - 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 slowcoding 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)]. Conclusion: The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation. KW - Coronary heart disease KW - Myocardial infarction KW - Dehydrogenase KW - Genotypes KW - Relative validity KW - Drinking habits KW - EPIC-Potsdam Study KW - German part KW - Case cohort KW - Stroke KW - Reproducibility PY - 2012 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-633710 DO - https://doi.org/10.1371/journal.pone.0032176 SN - 1932-6203 N1 - The recruitment phase of the EPIC-Potsdam Study was supported by the Federal Ministry of Science, Germany (01 EA 9401), and the European Union (SOC 95201408 05F02). The follow-up was supported by the German Cancer Aid (70-2488-Ha I) and the European Community (SOC 98200769 05F02). VL - 7 IS - 2 SP - 1 EP - 11 PB - Public Library of Science (PLoS) CY - San Francisco, California, US AN - OPUS4-63371 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -