A total of 7 gene polymorphisms from DRD2 (rs1800497, rs1079597, rs1800498, rs1801028) and 5-HT2 A (rs6313, rs6311, rs6305) were genotyped for their association with schizophrenia.
This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.
Remarkably, alleles of <i>COMT</i> rs165774 (G), <i>DRD2</i> rs6277 (T), and <i>DRD3</i> rs6280 (C) were associated with raised predisposition to schizophrenia (all <i>P</i><0.001).
Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.
In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia.
The relationships between DRD2 and clinical phenotypes are of particular interest because DRD2 has been shown to associate with treatment response and prefrontal dopamine transmission.Glatt et al. reported significant associations between schizophrenia and DRD2 variants (two single-nucleotide polymorphisms (SNPs) rs1079727 and rs2283265, and two haplotypes, block 3 (rs1079727(A)-rs2440390(C)-rs2283265(G)) and block 4 (rs1801028(G)-rs1110977(A)-rs1124492(C)-rs2734841 (T))) in 2408 Han Chinese individuals in Taiwan.
In conclusion, the G allele of DRD2 Ser311Cys polymorphism involves a potential risk factor for schizophrenia in Asian populations, especially in the Japanese population.
Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders: Ser311Cys polymorphisms of the dopamine D2-receptor gene and schizophrenia.
We did not find a significant effect of rs1801028, but we did find significant evidence for association of schizophrenia with two multi-marker haplotypes spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs (Ps<0.05).
Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds ratio=1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets.
The Cys allele of the DRD2 Ser311Cys polymorphism has a dominant effect on risk for schizophrenia: evidence from fixed- and random-effects meta-analyses.Am.J. Med.Genet.B. Neuropsychiatr.Genet.141, 149-154.]).
Though no association was found between the TaqIA polymorphism and schizophrenia, a haplotype-wise analysis revealed a lower frequency of the T-C (C957T-TaqIA) haplotype in patients (p=0.02).
One hundred thirty one outpatients in stable remission meeting the DSMIV criteria for schizophrenia spectrum disorders and receiving long-term maintenance therapy with haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms.
We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.
The present study was conducted to resolve discrepancies between the existing meta-analyses, and provide more comprehensive and accurate estimates of the nature and magnitude of the influence of the Ser311Cys polymorphism on risk for schizophrenia.
Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.
Meta-analyses of pooled ORs support association of schizophrenia to the Ser311Cys polymorphism in DRD2 and the T102C polymorphism in HTR2A, and of attention deficit hyperactivity disorder to the 48-bp repeat in DRD4.