Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians.
Alcoholism is one of a group of common psychiatric diseases which are well-defined clinically and strongly influenced genetically, but which are likely to be highly heterogeneous in causation, genetically and otherwise. Dopamine is a key neurotransmitter in drug-mediated reinforcement. Based on association studies with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to be the "Reward Deficiency Syndrome Gene." Ser311Cys, a naturally occurring variant which largely inactivates transduction after D2 receptor activation, was abundant (0.16) in a Southwestern American Indian population we studied. Therefore, we were able to provide a critical test of the D2 hypothesis of vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs, from large families. The result is that neither alcoholism, substance use disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when the 15 Cys311/Cys311 homozygous individuals are compared to others. Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder.
Goldman
D
D
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852, USA.
Urbanek
M
M
Guenther
D
D
Robin
R
R
Long
J C
JC
D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D001130:Arizona / Q000453:epidemiology; D004198:Disease Susceptibility; D005006:Ethnicity / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D015810:Linkage Disequilibrium; D009679:Nuclear Family; D017354:Point Mutation; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012201:Reward; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D019966:Substance-Related Disorders / Q000208:ethnology / Q000235:genetics*
D017448:Receptors, Dopamine D2