title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan a_yokoyama@kurihama1.hosp.go.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Department of Health Promotion, National Institute of Public Health, Saitama 351-0104, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan Department of Geriatric Medicine, Kyorin University Hospital, Tokyo 181-8611, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kimura
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
authors.affiliation: National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000097:blood / Q000150:complications / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics; D048909:Diabetes Complications / Q000235:genetics; D005838:Genotype; D006801:Humans; D007662:Ketosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial