Association of the ADHIB*3 allele with alcohol-related phenotypes in Trinidad.
BACKGROUND
Two of the class I alcohol dehydrogenase (ADH) genes located on chromosome 4 (ADH1B and ADH1C) encode for multiple isozymes that differ in their kinetic properties. At the ADH1B locus, 3 polymorphisms are present (ADH1B(*)1, ADH1B(*)2, ADH1B(*)3). ADH1B(*)2 (found mostly in individuals of East Asian and Jewish descent) and ADH1B(*)3 (found mostly in individuals of African decent) alleles encode for a more active enzyme variants than ADH1B(*)1 and the presence of these alleles has been associated with protection from alcohol dependence. The relationship between these alleles and alcohol-associated phenotypes has not been previously investigated in individuals living in the Caribbean.


METHODS
One hundred thirty-three alcohol-dependent individuals of either East Indian or African ancestry and 98 controls matched by age, sex, education, and ethnicity participated in the study. A structured interview [the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)] was used to gather information on demographics, psychiatric diagnoses, personal drinking, and drug use history. Leukocyte DNA extracted from a blood sample obtained from each participant was genotyped at the ADH1B locus. Serum levels of the liver enzymes alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) as well as the presence of HIV, hepatitis B surface antigen, and antihepatitis C virus antibody were also assayed. The specific aim of the study was to investigate the associations between ADH1B alleles and alcohol dependence, drinking history, and liver function in individuals from the 2 major ethnic groups of Trinidad (individuals of African and East Indian ancestry).


RESULTS
Twenty-eight of the Afro-Trinidadian (Afro-TT) participants (41%) and 1 Indo-Trinidadian (Indo-TT) (>1%) had at least 1 ADH1B(*)3 allele and 3 Afro-TT were homozygous for the allele. African participants with at least 1 ADH1B(*)3 allele were found to be significantly less likely to be alcohol dependent (p<0.018), and to have lower alcohol consumption levels (p<0.05). Among those participants who were alcohol dependent, ADH1B(*)3 was associated with significantly higher levels of ALT (p<0.05).


CONCLUSIONS
This study suggests, in this sample of Trinidadians, that the ADH1B(*)3 allele is associated with protection from the development of alcoholism but is also associated with enhanced risk for elevated serum ALT levels in those individuals who do become alcohol dependent.
Ehlers
Cindy L
CL
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California, USA. cindye@scripps.edu
Montane-Jaime
Karelia
K
Moore
Shelly
S
Shafe
Samuel
S
Joseph
Roma
R
Carr
Lucinda G
LG
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology; D019973:Alcohol-Related Disorders / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology; D000483:Alleles; D001219:Aspartate Aminotransferases / Q000097:blood; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D014300:Trinidad and Tobago / Q000208:ethnology; D044465:White People / Q000235:genetics
C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase