Association of a Genetic Polymorphism of the Alcohol-Metabolizing Enzyme ADH1C with Alcohol Dependence: Results of a Case-Control Study (original) (raw)
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A Preliminary Data: Distribution of ADH1C Genotypes and Alleles in Turkish Alcoholic Subjects
group (23%) compared to that of the alcohol-dependents (42%, p ! 0.0001). We obtained no statistically significant difference among the ADH1C genotype groups regarding age. Conclusions: These findings suggest that a significantly higher presence of ADH1C * 2 allele is associated with alcohol dependence in a Turkish population. Studies with other related polymorphisms are needed to more precisely estimate the association of alcohol dependence with ADH1C .
Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis
Human Molecular Genetics, 2006
Linkage evidence indicated that gene(s) located on chromosome 4q, in the region of the alcohol dehydrogenase (ADH ) genes, affected risk for alcoholism. We genotyped 110 single nucleotide polymorphisms (SNPs) across the seven ADH genes and analyzed their association with alcoholism in a set of families with multiple alcoholic members, using the pedigree disequilibrium test. There was strong evidence that variations in ADH4 are associated with alcoholism: 12 SNPs were significantly associated. The region of strongest association ran from intron 1 to 19.5 kb beyond the 3 0 end of the gene. Haplotype tag SNPs were selected for the block in the ADH4 gene that provided evidence of association and subsequently used in association analysis; the haplotype was significantly associated with alcoholism (P 5 0.01) There was weaker evidence that variations in ADH1A and ADH1B might also play a role in modifying risk. Among African-Americans, there was evidence that the ADH1B * 3 allele was protective.
Alcoholism: Clinical and Experimental Research, 2006
Background: Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations.
ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Human Molecular Genetics, 2009
We have previously found that variation in alcohol metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath alcohol concentrations after an alcohol challenge. In vivo alcohol metabolism was modelled with three parameters that identified the absorption and rise of alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting alcohol metabolism did not correspond to those reported to affect alcohol dependence or alcohol-related disease. The combined SNP associations with early-and late-stage metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo alcohol metabolism linked to this region is yet to be explained.
Alcoholism-clinical and Experimental Research, 2008
The genes coding for ethanol metabolism enzymes [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied for their influence on the risk to develop alcohol dependence (AD). However, the relation between polymorphisms of these metabolism genes and AD in Caucasian subjects has not been clearly established. The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence.
Genetics of Alcohol Use in Humans: An Overview
… JOURNAL OF HUMAN …, 2008
Alcoholism is an extremely complex disease for which no generally accepted definition exists. There is a complex interaction between the socio-environmental context, the individual at risk, and the availability of alcohol. The result of family, twin and adoption studies suggest a significant genetic predisposition to the disease. Identifying novel genetic risk factors for common diseases is a global challenge in the post genomic era. Recent molecular genetic research into the causes of alcoholism has drawn attention to the potential role of alcohol and acetaldehyde metabolizing enzymes. Functional polymorphisms have been observed at various genes encoding these enzyme proteins that act as one of the biological determinants significantly influencing drinking behavior and the development of alcoholism and alcohol-induced organ damage. Most ethanol elimination occurs by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) systems via oxidation of ethanol to acetaldehyde and acetic acid. However, the legacy of alcoholism among certain ethnic groups suggests that genetic factors can increase an individual's vulnerability for this disease. An association study in patient cohorts and controls, from large populations involving whole genome scans, is the preferred approach for complex traits. To understand the molecular epidemiology and role of cofactors in alcoholism the standard phenotype-genotype correlation may be a useful tool. The present paper reviews various aspects of alcoholism including both the behavioural and molecular etiologies.
Human Genetics, 2003
Enzymes encoded by two gene families, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current study, variants at ADH1B(previously ADH2), ADH1C (pre-viously ADH3), and ALDH2 were assayed in DNA extracts from participants belonging to a Southwest American Indian tribe (n=490) with a high prevalence of alcoholism. Each subject underwent a clinical interview for diagnosis of alcohol dependence, as well as evaluation of intermediate phenotypes such as binge drinking and flushing response to alcohol consumption. Detailed haplotypes were constructed and tested against alcohol dependence and related intermediate phenotypes using both association and linkage analysis. ADH and ALDH variants were also assayed in three Asian and one African population (no clinical data) in order to provide an evolutionary context for the haplotype data. Both linkage and association analysis identified several ADH1C alleles and a neighboring microsatellite marker that affected risk of alcohol dependence and were also related to binge drinking. These data strengthen the support for ADH as a candidate locus for alcohol dependence and suggest further productive study.