title: ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago.
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.
authors.affiliation: Department of Pharmacology, University of the West Indies, St Augustine, Trinidad and Tobago.
authors.forename: Karelia
authors.initials: K
authors.lastname: Montane-Jaime
authors.forename: Shelley
authors.initials: S
authors.lastname: Moore
authors.forename: Samuel
authors.initials: S
authors.lastname: Shafe
authors.forename: Roma
authors.initials: R
authors.lastname: Joseph
authors.forename: Helene
authors.initials: H
authors.lastname: Crooks
authors.forename: Lucinda
authors.initials: L
authors.lastname: Carr
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Ehlers
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D044383:Black People / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014300:Trinidad and Tobago; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase