The Ser9Gly polymorphism in dopamine D3 receptor gene (DRD3) was considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive.

To determine whether the DRD3 Ser9Gly polymorphism is associated with schizophrenia or influences its psychopathological symptoms in Han Chinese population.

We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS) in 128 acutely exacerbated schizophrenic in-patients. Genotyping of Ser9Gly polymorphism was performed with a polymerase chain reaction restriction fragment length polymorphism method and reconfirmed by a direct sequencing technique.

No significant difference was found between either patients with schizophrenia or with more homogeneous schizophrenic subgroups and healthy controls in genotype distributions and allele frequencies for the DRD3 Ser9Gly polymorphism. Similarly, DRD3 Ser9Gly genotype differences failed to reach significance in PANSS global, positive, negative and general symptoms scores. There is a trend (P = 0.064) towards higher PANSS positive symptoms scores in subjects carrying the Gly/Gly genotype.

This study does not support the role of DRD3 Ser9Gly polymorphism in increasing genetic risk for schizophrenia in Han Chinese population. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies are warranted to investigate the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics.