Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians

Am J Med Genet. 1997 Jul 25;74(4):386-94. doi: 10.1002/(sici)1096-8628(19970725)74:4<386::aid-ajmg9>3.0.co;2-n.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcoholism / ethnology
  • Alcoholism / genetics*
  • Alleles
  • Arizona / epidemiology
  • Disease Susceptibility
  • Ethnicity / genetics
  • Genetic Variation
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Indians, North American / genetics*
  • Linkage Disequilibrium
  • Nuclear Family
  • Point Mutation*
  • Receptors, Dopamine D2 / genetics*
  • Reward
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*
  • Substance-Related Disorders / ethnology
  • Substance-Related Disorders / genetics*

Substances

  • Receptors, Dopamine D2