Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes and Alcoholic Ketosis Are Associated with the Serum Uric Acid Level in Japanese Alcoholic Men.

Aims: To identify determinants of hyperuricemia in alcoholics. Methods: The serum uric acid (UA) levels of 1759 Japanese alcoholic men (= 40 years) were measured on their first visit or within 3 days after admission; ADH1B and ALDH2 genotyping on blood DNA samples were performed. Dipstick urinalyses for ketonuria and serum UA measurements were simultaneously performed for 621 men on their first visit. Results: Serum UA levels of > 416 mu mol/l (7.0 mg/dl) and = 535 mu mol/l (9.0 mg/dl) were observed in 30.4 and 7.8% of the subjects, respectively. Ketonuria was positive in 35.9% of the subjects, and a multivariate analysis revealed that the ketosis level was positively associated with the UA level. The presence of the ADH1B* 2 allele and the ALDH2* 1/* 1 genotype increased the odds ratio (OR; 95% confidence interval) among subjects with a high UA level of > 416 mu mol/l (vs. = 416 mu mol/l; 2.04 [1.58-2.65] and 1.48 [1.09-2.01], respectively) and those with a high UA level of = 535 mu mol/l (vs. = 416 mu mol/l; 2.29 [1.42-3.71] and 3.03 [1.51-6.08], respectively). The ADH1B* 2 plus ALDH2* 1/ * 1 combination yielded the highest ORs (2.86 [1.61-5.10] and 6.21 [1.49-25.88] for a UA level of > 416 mu mol/l and = 535 mu mol/l, respectively), compared with the ADH1B* 1/* 1 plus ALDH2* 1/* 2 combination. The presence of diabetes and the consumption of Japanese sake rather than beer were negatively associated with the UA levels. Conclusions: The faster metabolism of ethanol and acetaldehyde by the ADH1B* 2 allele and ALDH2* 1/* 1 genotype and higher ketosis levels were associated with higher UA levels in alcoholics, while diabetes and the consumption of sake were negative determinants.