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Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

ABSTRACT: 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.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.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).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.

SUBMITTER: Yokoyama A

PROVIDER: S-EPMC4540432 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

Yokoyama Akira A Yokoyama Tetsuji T Matsui Toshifumi T Mizukami Takeshi T Kimura Mitsuru M Matsushita Sachio S Higuchi Susumu S Maruyama Katsuya K

PloS one 20150818 8

<h4>Background</h4>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 a ...[more]

PMID: 26284938

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Project description:BACKGROUND:Alcohol consumption and oxidative stress are well-known risk factors for developing atrial fibrillation (AF). Single nucleotide polymorphisms (SNPs) of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes encoding enzymes of alcohol and reactive aldehyde metabolism, respectively, are prevalent among East Asians. Here, we examined whether these SNPs were associated with AF in Japanese patients. METHODS AND RESULTS:Five hundred seventy-seven Japanese patients with AF undergoing catheter ablation and 1935 controls at Hiroshima University Hospital were studied. Alcohol consumption habits, medical history, electrocardiogram (EKG), electrophysiology and cardiac echocardiography were reviewed. Patients were also genotyped for ALDH2 (rs671) and ADH1B (rs1229984). A significant linear correlation was found between ALDH2 genotype and mean alcohol intake (P?=?1.7?×?10-6). Further, ALDH2 (rs671) was associated with AF (P?=?7.6?×?10-4, odds ratio [OR]?=?0.6). Frequency of the ALDH2 SNP allele A which limits acetaldehyde metabolism was lower in patients with AF (18.8%) than in controls (23.5%). In contrast, we found that the frequencies of the ADH1B SNP genotypes were similar in patients with AF and in controls. Subset analysis among the 182 patients with lone AF and 914 controls (control II) (<60 years of age and without hypertension), both ALDH2 and ADH1B SNPs were significantly associated with AF (P?=?0.013, OR?=?0.7; P?=?0.0007, OR?=?1.4, respectively). The frequency of the dysfunctional allele A of ALDH2 was significantly lower and the dysfunctional allele G of ADH1B was significantly higher in patients with lone AF than in control II (ALDH2 A allele frequency?=?0.176 vs 0.235, OR?=?1.3, P?=?0.013, ADH1B SNP G allele frequency?=?0.286 vs 0.220, OR?=?1.4, P?=?0.0007). CONCLUSIONS:When considering all patients enrolled, the dysfunctional ALDH2 allele was negatively associated with AF. When examining a subset of patients with lone AF, the dysfunctional ALDH2 allele was negatively associated with AF and the slower metabolizing ADH1B allele was positively associated with AF. Hence, prolonged metabolic conversion of alcohol to acetaldehyde may be associated with the occurrence of AF in the Japanese and other East Asian populations.

Project description:The mutant allele (*2) of aldehyde dehydrogenase type 2 (ALDH2) caused by a single nucleotide variant (rs671) inhibits enzymatic activity and is associated with multiple diseases. In recent years, an explosive number of original studies and meta-analyses have been conducted to examine the associations of ALDH2 rs671 polymorphism with diseases. Due to conflicting results, the overall associations of ALDH2 rs671 polymorphism and multiple diseases remain unclear. A quantitative umbrella review will be conducted on meta-analyses of genetic association studies to examine the pleiotropic effects of ALDH2 rs671, mainly including cardio-cerebral vascular disease, diabetes mellitus, cancer, neurodegenerative disease, and alcohol-induced medical disease. A search of relevant literature according to comprehensive search strategies will be performed on studies published before July 1st, 2022 in PubMed, MEDLINE Ovid, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Study selection, data extraction, methodology quality assessment, and strength of evidence assessment will be conducted by two reviewers independently and in duplicate. Included meta-analyses will be grouped by outcomes. Data conflicts and overlap between meta-analyses will be managed through updated standardized and customized methods including the calculation of CCA for study selection reference, application of Doi plots to assess small-study effects and others. Evidence from included meta-analyses will be quantitatively synthesized by overlap-corrected analyses and meta-analysis using primary studies. This umbrella review is expected to generate systematic evidence on the association between ALDH2 rs671 and diseases. Specific approaches were developed to address key challenges in conducting an umbrella review, including assessment tools of methodology and evidence quality of meta-analyses, methods to manage overlap between meta-analyses, a "stop-light" plot to summarize key findings. These approaches provide applicable methods for future umbrella reviews of meta-analyses on genetic association studies. CRD42021223812.

Dataset Information

Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

Publications

Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

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