D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism.
As the dopaminergic and GABAergic systems have been implicated in alcohol-related behaviors, variants of the D2 dopamine receptor (DRD2) and GABA(A) receptor beta3 subunit (GABRB3) genes were determined in a population-based association study of Caucasian non-alcoholic and alcoholic subjects. In severe alcoholics, compared to non-alcoholics, a significant increase was found in the prevalence (P = 1.7 x 10(-5)) and frequency (P = 1.6 x 10(-5)) of the DRD2 minor (A1) allele. Moreover, a significant progressive increase was observed in A1 allelic prevalence (P = 3.1 x 10(-6)) and frequency (P = 2.7 x 10(-6)) in the order of non-alcoholics, less severe and severe alcoholics. In severe alcoholics, compared to non-alcoholics, a significant decrease was found in the prevalence (P = 4.5 x 10(-3)) and frequency (P = 2.7 x 10(-2)) of the GABRB3 major (G1) allele. Furthermore, a significant progressive decrease was noted in G1 allelic prevalence (P = 2.4 x 10(-3)) and frequency (P = 1.9 x 10(-2)) in non-alcoholics, less severe and severe alcoholics, respectively. In sum, in the same population of non-alcoholics and alcoholics studied, variants of both the DRD2 and GABRB3 genes independently contribute to the risk for alcoholism, with the DRD2 variants revealing a stronger effect than the GABRB3 variants. However, when the DRD2 and the GABRB3 variants are combined, the risk for alcoholism is more robust than when these variants are considered separately.
Noble
E P
EP
Alcohol Research Center and Department of Psychiatry and Biobehavioral Sciences, UCLA, Neuropsychiatric Institute, Los Angeles, CA 90024-1759, USA. epnoble@ucla.edu
Zhang
X
X
Ritchie
T
T
Lawford
B R
BR
Grosser
S C
SC
Young
R M
RM
Sparkes
R S
RS
D000328:Adult; D000437:Alcoholism / Q000145:classification / Q000235:genetics* / Q000534:rehabilitation; D000483:Alleles; D001315:Australia; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011379:Prognosis; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D012306:Risk
D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A