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The cardioprotective effect of ethanol has been suggested to be linked to one of the ethanol metabolizing enzymes (ADH1C), which constitutes a high Vmax and a low Vmax variant. This has been demonstrated in some studies, while others have not been able to replicate the findings. The aim of the present study was to investigate the relation between the different ADH1C genotypes, death from coronary heart disease (CHD) and alcohol in a material larger than the previously published studies. Eight hundred CHD deaths as well as 1303 controls were genotyped for the high Vmax (?1) and the low Vmax (?2) ADH1C variant. Information of alcohol use was available for all subjects. Multiple logistic regression analyses was used to study if the decreased risk of death from CHD in alcohol consuming subjects was more pronounced in subjects homozygous for the ?2 allele (?2?2 subjects) compared to ?1?1 and ?1?2 subjects. The odds ratio (OR) for death from CHD in alcohol consumers compared to abstainers was similar in the genotype groups, i.e., 0.62 (95% CI: 0.43e0.88) in ?1?1 subjects and 0.62 (95% CI: 0.42e0.91) in ?2?2 subjects. Also when stratifying the results by gender and when dividing alcohol consumers into different alcohol consumption groups, there was no difference in the OR between the different genotype groups. This study, which included the largest study group published so far, failed to find any link between the ADH1C genotype and the cardioprotective effects of alcohol. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this paper is to study polymorphism in the TH, ADH1B, ADH1C, ALDH2 and CYP2E1 genes so as to ascertain whether it is associated with excessive consumption of alcohol. The SNPs rs6356 of TH, rs1229984, rs2066702 of ADH1B; rs698, rs1693482 of ADH1C; rs671 of ALDH2; rs72559710, rs55897648, rs6413419, rs3813867, rs2031920, rs6413432 of CYP2E1 were studied in a sample of 172 high-level patients and 150 fully non-drinkers controls. Genotyping was performed using Rt-PCR with Taqman probes. SNPs located at ALDH2 and CYP2E1 showed no heterozygosity. Frequency distribution showed significant differences between the two groups studied for loci TH and ADH1B. The genotype Val/Val of TH locus increased in risk 1.988 times (95% CI: 1.006–3.930) that the subjects carrying the genotype Met/Met; and the genotype ADH1B*1/*1 of ADH1B locus increased in risk 3.811 times (CI: 1.660–8.749) that the subjects carrying the genotype ADH1B*1/*2. Alleles Val and ADH1B*1 may therefore increase the risk of the onset and development of this illness. [Copyright &y& Elsevier]

Abstract: Purpose: Recent epidemiological studies demonstrated that alcohol dehydrogenase 1C (ADH1C) alleles that result in acetaldehyde accumulation in the cells can enhance a drinker’s risk of developing alcohol related cancer in a variety of tissues. The published data on the association between ADH1C alleles and breast cancer occurrence in Caucasians have led to in contradictory results. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. Methods: A total of 12 studies were identified to the meta-analysis, including 6159 cases and 5732 controls from Caucasians. The pooled odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with ADH1C genotype was estimated. Results: Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (ADH1C1-2 vs. ADH1C2-2 : OR 1.07, 95% CI 0.97–1.19; ADH1C1-1 vs. ADH1C2-2 : OR 1.16, 95% CI 0.94–1.43; dominant model: OR 1.07, 95% CI 0.97–1.18; recessive model: OR 1.06, 95% CI 0.93–1.20). There was no evidence for the association between ADH1C genotype and breast cancer risk in subgroup analyses based on design of experiment and menopausal status. And for the additive model, individuals carrying the ADH1C*1 allele were not significantly associated with increased risk to breast cancer (OR 1.01, 95% CI 0.97–1.06). Conclusion: This meta-analysis suggests that ADH1C polymorphism may not be associated with breast cancer development in Caucasians. And larger scale primary studies are required to further evaluate the interaction of ADH1C polymorphism and breast cancer risk in specific populations. [Copyright &y& Elsevier]

Abstract: Alcoholism is a complex genetically influenced disorder which refers to alcohol abuse and alcohol dependence. There are controversial results on the role of gene polymorphisms in alcohol dependence in the literature. Differences in population groups and selective inclusion criteria for alcohol dependence may affect results. In this study, we investigated the role of ADH1B Arg48His (rs1229984) and, ADH1C Ile350Val (rs698) gene polymorphisms in Turkish population. 100 healthy volunteers and 75 patients who were admitted to Ege University Alcohol Dependence Unit enrolled in the study. We found significant increase both in ADH1B (Arg48His) polymorphism Arg allele and Arg/Arg genotype frequency in patients. No profound connection between alcohol dependence and ADH1C Ile350Val gene polymorphism was detected. Alcohol dependence is an important health problem that depends on many genetic and environmental factors but we think that it is possible to interpret genetic risk for developing early diagnostic methods and treatment strategies by comprehensive linkage and association studies. [Copyright &y& Elsevier]

Abstract: Introduction: Moderate alcohol consumption is protective against cardiovascular disease (CAD). ADHs are major enzymes of alcohol metabolism. A polymorphism in the alcohol dehydrogenases 1C gene (ADH1C) was reportedly associated with the protective effect of alcohol consumption on CAD risk and risk factor levels. Aims: The aim of our study was to investigate whether the association of alcohol consumption with metabolic risk factors for CAD is related to ADH1C variants. Methods: IMMIDIET is a cross-sectional study of 974 healthy male–female pairs living together, randomly recruited in Belgium, Italy and England. The rs698 ADH1C polymorphism was genotyped. A 1-year recall food frequency questionnaire was used to estimate alcohol intake. Results: The intake of alcohol did not vary in relation to ADH1C genotypes. BMI, waist circumference (WC), waist-to-hip ratio, blood pressure, HDL or total cholesterol, triglycerides and FVII:ag levels were positively associated with alcohol intake in men (multivariate ANOVA). Regression coefficient for alcohol and BMI or WC was progressively higher in heterozygotes and gamma 2 homozygotes as compared to gamma 1 homozygotes (p =0.006 and p =0.03 for interaction, respectively). No interaction was found for other risk factors. In women, alcohol intake was positively associated with HDL, LDL and FVII:ag levels but no interaction was found between ADH1C polymorphism and any risk factor. Conclusion: Regulation of ADH1C genotype on the association between alcohol consumption, BMI and WC was found in men from different European countries. In men homozygous for the gamma 2 alleles, intake of alcohol was positively associated with both BMI and WC values. [Copyright &y& Elsevier]

Abstract: Variants in alcohol dehydrogenase (ADH) genes differ between ethnic groups and have, in some studies, been found to be associated with alcohol dependence and alcoholic liver disease. This study sought to determine whether an association exists between ADH (ADH1C previously ADH3, ADH1B*2 previously ADH2*2) genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT). One hundred and forty-five alcohol-dependent individuals of both East Indian (Indo-TT) and African (Afro-TT) ancestry, and 108 controls matched by age, sex, and education participated in the study. Serum levels of alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) as well as presence of HIV, hepatitis B surface antigen, and anti-hepatitis C virus antibody were determined. There was a significant difference in the distribution of ADH1C allele polymorphisms between the ethnic groups (P <.0001). Forty-three percent of the Indo-TT were found to have one ADH1C*2 allele and 5% were homozygous, whereas, only 23% of Afro-TT had one allele and one was homozygous. Only three individuals had an ADH1B*2 allele (one Indo-TT alcohol dependent, two Indo-TT controls). The ADH1C*2 allele was significantly associated with alcohol dependence overall and within Indo-TT ancestry, however, it was not associated with current or heaviest alcohol consumption levels. Individuals with at least one ADH1C*2 allele also had significantly elevated levels of ALP (P <.02) and GGT (P <.02) as compared to individuals homozygous for ADH1C*. Additionally, GGT levels were also found to be elevated (P <.02) within Indo-TT alcohol dependents with at least one ADH1C*2 allele but not within the Afro-TT alcohol dependents with that allele. A linear regression that included alcohol dependence and levels of alcohol consumption confirmed that levels of serum GGT were significantly associated with the ADH1C*2 genotype. These results suggest that ADH1C polymorphisms are associated with alcohol dependence and alcohol associated elevations of liver enzymes in a population with a low frequency of ADH1B2 alleles. [Copyright &y& Elsevier]

Abstract: We previously demonstrated that a functional polymorphism in alcohol dehydrogenase type 1C (ADH1C, also known as ADH3) modifies the association between moderate alcohol consumption and high-density lipoprotein (HDL) levels and risk of myocardial infarction among older men. In this study, we investigated the effect of the ADH1C γ1 and γ2 alleles on the relationship between alcohol consumption and HDL levels among four populations with varied exposure to endogenous and exogenous estrogens: premenopausal women, middle-to-older aged men, postmenopausal women currently using postmenopausal hormones (PMH) and postmenopausal women not currently using PMH. We observed an interaction between moderate alcohol consumption and ADH1C genotype on HDL level that was similar among middle-to-older aged men and postmenopausal women not using PMH. Among the moderate drinkers (approximately a half a drink per day for women and a full drink per day for men), there was a significant 5.3mg/dL (P =0.02) higher level of multivariate adjusted HDL level comparing the γ2 homozygotes (slow oxidizers) to the γ1 homozygotes (fast oxidizers). This interaction was not present among premenopausal women or postmenopausal women using PMH, who had higher overall HDL levels irrespective of alcohol consumption. Our results confirm that ADH1C genotype modifies the association between alcohol consumption and HDL levels among men and postmenopausal women not using PMH who drink moderately. However, this was not observed among individuals with estrogen-elevated HDL levels, specifically premenopausal women and postmenopausal women taking PMH, suggesting that these populations may benefit less from alcohol consumption with respect to coronary heart disease. [Copyright &y& Elsevier]

Abstract: Alcohol dehydrogenase 1C (ADH1C or ADH3) genotype reportedly modifies the association between alcohol consumption and coronary heart disease (CHD) risk, as well as influencing plasma high-density lipoprotein (HDL) levels [Hines LM, Stampfer MJ, Ma J, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549–55]. This relationship has been examined in a sample of middle-aged (50–61 years) men (total of 2773 with 220 CHD events), participating in the prospective Second Northwick Park Heart Study (NPHS II). Alcohol consumption was assessed by questionnaire as the number of units consumed in the previous week. Drinkers experienced lower CHD risk than abstainers [hazard ratio (HR) 0.73 (95% confidence intervals (CI) 0.53, 0.99; p =0.04)] and had significantly higher HDL and apolipoprotein (apo)AI concentrations (both p &#60;0.0001) and a lower fibrinogen (p =0.02). Overall, there was no effect of ADHC1 γ1>γ2 genotype on plasma levels of HDL, apoAI or fibrinogen or on CHD risk. To consider whether the effect of alcohol consumption on risk was modulated by genotype, the men were divided into abstainers, modest drinkers (1–3units/week) and those who consumed more than 3units/week. Significant alcohol:genotype interaction on CHD risk was observed (p =0.02), with γ2 homozygotes, who were modest drinkers, displaying 78% CHD risk reduction compared to γ1 homozygotes (HR=0.22, 95% CI 0.05–0.94). There was, however, no association between genotype and apoAI, HDL or fibrinogen and this was not altered when alcohol intake was considered. These findings confirm that the cardiovascular benefit of modest alcohol consumption. ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported. [Copyright &y& Elsevier]

ADH1C was downregulated during inflammation, and its increased expression could inhibit the activation of STAT1/NF-κB pathway, thereby alleviating the secretion of proinflammatory cytokines. [Display omitted] Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease caused by an interaction of genetics, immune responses, and environmental factors. However, the precise pathogenesis of UC remains poorly understood. The aim of the present study was to explore the potential target genes implicated in UC and to elucidate its underlying pathogenic mechanism. Firstly, three UC-associated microarray datasets (GSE75214, GSE87466, and GSE92517) were obtained to screen the differentially expressed genes (DEGs). As a result, alcohol dehydrogenase 1C (ADH1C) was the most significantly downregulated DEG in UC. We confirmed that ADH1C was downregulated in colonic tissue taken from patients with UC and colitis mice. Moreover, ADH1C expression was also decreased in colonic cell lines (NCM460 and HT29) treated with mixed proinflammatory cytokines (TNF-α, IFN-γ, IL-1β). Interestingly, we found that overexpression of ADH1C could distinctly decrease the production of IL-6 and IL-8. To elucidate the molecular mechanism of ADH1C in UC, gene set enrichment analysis (GSEA) was performed and demonstrated that immune-related pathways were mainly enriched in the low ADH1C group. Further studies displayed that STAT1/NF-κB pathway was activated in colitis mice and inflammatory cell model. Importantly, overexpression of ADH1C could suppress the phosphorylation of STAT1 and IκB. Therefore, ADH1C might regulate inflammatory responses through STAT1/NF-κB pathway. In conclusion, ADH1C was downregulated during inflammation, and its increased expression could inhibit the activation of STAT1/NF-κB pathway, thereby alleviating the secretion of IL-6 and IL-8. These findings indicate that ADH1C may be a potential therapeutic target for UC therapy. [ABSTRACT FROM AUTHOR]

Multiple genes have been implicated in Parkinson's disease (PD), including causal gene variants and risk variants typically identified using genome-wide association studies. Variants in the alcohol dehydrogenase genes ADH1C and ADH1B are among the genes that have been associated with PD, suggesting that this family of genes may be important in PD. As part of the International Parkinson's Disease Genomics Consortium's efforts to scrutinize previously reported risk factors for PD, we explored genetic variation in the alcohol dehydrogenase genes ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, and ADH7 using imputed genome-wide association study data from 15,097 cases and 17,337 healthy controls. Rare-variant association tests and single-variant score tests did not show any statistically significant association of alcohol dehydrogenase genetic variation with the risk for PD. [ABSTRACT FROM AUTHOR]