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Effect of Alcohol Consumption and Alcohol Dehydrogenase 1C (ADH1C) Polymorphisms on Total Plasma Homocysteine Levels
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BACKGROUND: Evidence supports that an elevated level of total plasma homocysteine (tHcy) signifies a breakdown in the methionine-homocysteine cycle. This may result in folate deficiency, DNA methylation and oxidative stress, all of which are potential mechanisms that may lead to cancer. Few studies examined the effects of alcohol consumption on tHcy levels. No studies considered polymorphisms in alcohol dehydrogenase 1C (ADH1C), a gene that encodes for an enzyme that metabolizes alcohol to acetaldehyde, a folate antagonist; ADH1C*1 encodes for an enzyme with a higher capacity to generate acetaldehyde than ADH1C*2. PURPOSE: This study examined the association between alcohol intake and risk of elevated tHcy while exploring a potential gene-environment interaction with polymorphisms in ADH1C. METHOD: This was a case-control study nested in a larger cross-sectional study funded by Canadian Institutes of Health Research. The target population was recruited from Kingston and Halifax from 2006 to 2008 and included 100 cases and 187 controls selected from healthy male and female subjects aged 20-50 years. Cases were defined as subjects with tHcy ≥ 10 mol/L and controls < 10 mol/L. Alcohol consumption was categorized into three groups: ≤12.0 g/day, 12.1–24.0 g/day, and >24.0 g/day. ADH1C was dichotomized by collapsing ADH1C*1/*2 and ADH1C*2/*2 into one group and examined against ADH1C*1/*1. RESULTS: Compared to ≤12.0 g/day, odds ratio (OR) for 12.1-24.0 g/day was 0.53 [95% confidence interval (CI), 0.25-1.13] and for >24.0 g/day was 1.19 (95% CI, 0.60-2.24), suggesting a J-shaped trend with risk of elevated tHcy. A reduced OR was observed for ADH1C*1/*1 (OR= 0.52, 95% CI, 0.27-1.03). The alcohol-ADH1C interaction was not statistically significant (p-value = 0.21), though a stronger J-shape trend was suggested in ADH1C*1/*1. Among consumers of ≤12.0 g/day, a reduced measure of effect was observed for ADH1C*1/*1 (OR= 0.44, 95% CI, 0.19-1.00). CONCLUSION: A J-shaped trend was suspected between risk of elevated tHcy and alcohol consumption. Additionally, a nonsignificant reduced effect of ADH1C*1/*1 on risk of elevated tHcy, with a more pronounced effect in the lowest group of alcohol consumption. This suggests that ADH1C may be associated to homocysteine through factors unrelated to alcohol intake.