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

Alcohol Alcohol. 2016 May;51(3):268-74. doi: 10.1093/alcalc/agv123. Epub 2015 Nov 4.

Abstract

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 μmol/l (7.0 mg/dl) and ≥535 μmol/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 μmol/l (vs. ≤416 μmol/l; 2.04 [1.58-2.65] and 1.48 [1.09-2.01], respectively) and those with a high UA level of ≥535 μmol/l (vs. ≤416 μmol/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 μmol/l and ≥535 μmol/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.

MeSH terms

  • Adult
  • Alcohol Dehydrogenase / genetics*
  • Alcoholism / blood
  • Alcoholism / complications
  • Alcoholism / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Alleles
  • Asian People / genetics
  • Diabetes Complications / genetics
  • Genotype
  • Humans
  • Ketosis / blood
  • Ketosis / complications
  • Ketosis / genetics*
  • Male
  • Middle Aged
  • Uric Acid / blood*

Substances

  • Uric Acid
  • ADH1B protein, human
  • Alcohol Dehydrogenase
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial