Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia

Hum Genet. 1996 Jun;97(6):714-9. doi: 10.1007/BF02346178.


We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.

Publication types

  • Clinical Trial
  • Meta-Analysis
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Antipsychotic Agents / therapeutic use
  • Base Sequence
  • Clozapine / therapeutic use
  • Disease Susceptibility
  • Gene Dosage
  • Gene Frequency
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3
  • Schizophrenia / drug therapy
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*


  • Antipsychotic Agents
  • DRD3 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Clozapine