Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu=Lys or Lys=Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g=day was −2.49 mg=dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His=His + ALDH2 Glu=Lys or Lys=Lys groups (−3.24 mg=dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His=His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu=Lys or Lys=Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.
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