Investigation of possible association between Ser9Gly polymorphism of the D3 dopaminergic receptor gene and response to typical antipsychotics in patients with schizophrenia

Abstract

Typical antipsychotics have a high affinity for dopamine receptors. It is therefore of interest to investigate such loci in pharmacogenetic studies on psychosis. We investigated the hypothesis that Ser9Gly polymorphism of the DRD3 gene may play a role in the differences in individual response to typical antipsychotics between schizophrenic patients. The sample was composed of 53 good responders and 59 poor ones. No significant differences between the good and poor responders were found in the allelic distribution (good responders: Ser9 61.32%, Gly9 38.67%; poor responders: Ser9 64.40%, Gly9 35.59%; odds ratio, OR = 0.88, 0.49 < OR < 1.56; chi2 = 0.23, 1 degree of freedom, df, p = 0.63) and genotype distribution (good responders: Ser9/Ser9 37.73%, Ser9/Gly9 47.16%, Gly9/Gly9 15.09%; poor responders: Ser9/Ser9 42.37%, Ser9/Gly9 44.06%, Gly9/Gly9 13.55%; chi2 = 0.25, 2 df, p = 0.88). Nor was there any association with homozygosity (good responders: homozygous: 52.82%, heterozygous: 47.16%; poor responders: homozygous: 55.92%, heterozygous: 44.06%; odds ratio, OR = 0.88, 0.39 < OR < 1.99; chi2 = 0.11, 1 df, p = 0.74). The results did not support the hypothesis that Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics in our sample of schizophrenics.

A review of psychiatric genetics research in the Brazilian population

“…Cordeiro et al did not find support for the hypothesis that the Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics. 68 In another study, Michelon et al found that the polymorphisms of the SLC6A4, glycogen synthase kinase-3beta, inositol polyphosphatase 1-phosphate, brain-derived neurotrophic factor and activator protein 2beta genes are not predictive factors for lithium prophylactic response in a sample of BPD type I patients. 69 Challenges for the improvement of psychiatric genetic studies in Brazil 1.…”

Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients

“…In the above‐mentioned studies, male gender, age at onset, shorter duration of illness, higher levels of positive and negative symptoms, and individual genetic differences have been reported to play a role in clinical responses to medications [Cordeiro et al, 2006; Semiz et al, 2007]. It is difficult to identify which factor is predominant due to inconsistent and somewhat contradictory results caused by heterogeneity of the disorder, specific subgroups of schizophrenic patients, and the effect of racial stratification.…”

“…However, studies focusing on ethnic differences in responsiveness to clozapine have revealed few genetic factors (that influence drug metabolism and molecular targets of drug action). However, the reasons why some patients fail to respond clinically despite taking therapeutic doses of medication remain largely unknown [Dubertret et al, 1998; Scharfetter et al, 1999; Wong et al, 2000; Bernard and Segman, 2006; Cordeiro et al, 2006].…”