A GSTP1 functional variant associated with cocaine dependence in a Brazilian population.
Cocaine dependence aetiology is complex and genetically influenced. We hypothesize that, for many users, efficient metabolism of cocaine and its toxic byproducts aids persistent cocaine use, such as that leading to dependence. The glutathione-S-transferases - in particular, GST-Pi - may be important in preventing cocaine and alcohol-induced oxidative damage. We genotyped a GST-Pi functional polymorphism (Ile105Val) in 654 male cocaine users and 572 controls from Brazil. Genotype and allele frequencies of Ile105Val differed significantly (chi = 6.74; P=0.03 and chi = 6.54; P = 0.01, respectively). Ile/Ile cocaine dependents had an OR = 1.31 (95%CI: 1.04-1.65), and Ile/Ile dependents consuming >50 units alcohol weekly an OR of 1.44 (95% CI:1.06-1.96). Population stratification was assessed and did not affect the results. These data require replication but do suggest that the high activity Ile105 GST-Pi allele may influence the aetiology and development of cocaine dependence.
Guindalini
Camila
C
MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK.
O'Gara
Colin
C
Laranjeira
Ronaldo
R
Collier
David
D
Castelo
Adauto
A
Vallada
Homero
H
Breen
Gerome
G
D000328:Adult; D000553:Ambulatory Care; D001938:Brazil; D003042:Cocaine; D019970:Cocaine-Related Disorders / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male
C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D003042:Cocaine