Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.
BACKGROUND
Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.


METHODS
The population consisted of 1806 Japanese alcoholic men (≥40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.


RESULTS
High serum levels of TG (≥150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99-1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28-0.49] and 0.51 [0.37-0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl) and HDL-C (≥100 mg/dl).


CONCLUSIONS
The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels.
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Akira
A
Yokoyama
Department of Health Promotion, National Institute of Public Health, Saitama, 351-0104, Japan.
Tetsuji
T
Yokoyama
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan; Department of Geriatric Medicine, Kyorin University Hospital, Tokyo, 181-8611, Japan.
Toshifumi
T
Matsui
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Takeshi
T
Mizukami
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Mitsuru
M
Kimura
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Sachio
S
Matsushita
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Susumu
S
Higuchi
National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, 239-0841, Japan.
Katsuya
K
Maruyama
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics; D057229:Alcoholics; D000437:Alcoholism / Q000097:blood* / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D014280:Triglycerides / Q000097:blood*
D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial