The influence on the schizophrenic symptoms by the DRD2Ser/Cys311 and −141C Ins/Del polymorphisms

Abstract

The hyperactivity of dopaminergic systems is one of the major etiological hypotheses of schizophrenia. The major support for this hypothesis is that effective antipsychotic drugs bind to dopamine receptors and improve acute schizophrenic symptoms. For this reason, we investigated the allelic association between schizophrenia and polymorphisms of the DRD2 genes for the Ser/Cys311 and -141C Ins/Del. The subjects were 190 schizophrenics (120 males and 70 females) and 103 normal controls (53 males and 50 females). There were no significant differences between the patients and controls in the allele frequencies and the frequencies of the genotypes. We found no statistical association between schizophrenia and polymorphisms of the DRD2 genes for the Ser/Cys311 and -141C Ins/Del. These results indicate that the DRD2 gene may not develop schizophrenia. Next, we examined whether the genotypes influence the symptoms of schizophrenia the using Positive and Negative Symptom Scale scores. The Ser/Cys patients exhibited significantly lower positive and negative symptom scores than Ser/Ser patients. Patients with Del/Del, Ins/Del, or Ins/Ins showed higher positive symptom scores in descending order. This result suggested that the Del allele worsens the positive symptoms. We concluded that the DRD2 receptor gene may not influence the onset of schizophrenia, but there is a strong possibility that the Cys311 and -141C Del have a significant influence on the symptoms of schizophrenia.

Family association study between DRD2 and DRD3 gene polymorphisms and schizophrenia in a Portuguese population

“…However, they are in agreement with case-control association studies carried out in different populations (Itokawa et al, 1993;Sasaki et al, 1996;Tanaka et al, 1996;Spurlock et al, 1998;Hori et al, 2001;Himei et al, 2002). Other authors also have obtained inconsistent results with association studies with the y141C InsyDel polymorphism at the DRD2 gene (Li et al, 1998;Breen et al, 1999;Jonsson et al, 1999;Himei et al, 2002).…”

“…Our findings for TaqI-A and Ser311Cys polymorphisms do not corroborate previous findings obtained with case-control association studies (Arinami et al, 1994(Arinami et al, , 1996 and meta-analysis (Jonsson et al, 2003a). However, they are in agreement with case-control association studies carried out in different populations (Itokawa et al, 1993;Sasaki et al, 1996;Tanaka et al, 1996;Spurlock et al, 1998;Hori et al, 2001;Himei et al, 2002). Other authors also have obtained inconsistent results with association studies with the y141C InsyDel polymorphism at the DRD2 gene (Li et al, 1998;Breen et al, 1999;Jonsson et al, 1999;Himei et al, 2002).…”

“…Several case-control studies have investigated the possible involvement of the DRD2 and DRD3 genes in schizophrenia, but the results are inconclusive (Dubertret et al, 1998;Spurlock et al, 1998;Williams et al, 1998;Kremer et al, 2000;Hori et al, 2001;Himei et al, 2002;Morimoto et al, 2002). However, meta-analyses have recently supported the involvement of the DRD2 and DRD3 genes in the pathogenesis of schizophrenia (Jonsson et al, 2003a,b).…”

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

“…Several studies have associated D 2 genetic variants with response to classical antipsychotics, [88][89][90][91][92] but also with response to clozapine, olanzapine (atypical antipsychotics) and risperidone (an atypical antipsychotic with strong D 2 binding). [93][94][95][96] In particular, the Del allele of a À141-C Ins/Del polymorphism was associated with lower improvement after antipsychotic treatment in two independent studies 88,89 (see Table 3).…”

“…[93][94][95][96] In particular, the Del allele of a À141-C Ins/Del polymorphism was associated with lower improvement after antipsychotic treatment in two independent studies 88,89 (see Table 3). Conflicting reports associate the À141-C Del allele with lower expression of the D2 receptor in vitro, 159 and higher D2 density in the striatum in vivo, 160 making it difficult to discern a plausible biological explanation for this finding.…”