Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence.
Anatomical, pharmacological and human post-mortem studies suggest the dopamine D3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zückerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).
Duaux
E
E
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Université René Descartes, Hôpital Sainte-Anne, Paris, France.
Gorwood
P
P
Griffon
N
N
Bourdel
M C
MC
Sautel
F
F
Sokoloff
P
P
Schwartz
J C
JC
Ades
J
J
Lôo
H
H
Poirier
M F
MF
D000328:Adult; D015252:Deoxyribonucleases, Type II Site-Specific; D005602:France; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009017:Morbidity; D009293:Opioid-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D010551:Personality / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012016:Reference Values
C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015252:Deoxyribonucleases, Type II Site-Specific; C060616:TGGCCA-specific type II deoxyribonucleases