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.
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.
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).
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.
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.
Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.
For AD+DD, the risk regions centered on TTC12 exon 3 [optimal individual haplotype simulated p (p(oihs)) = 0.000015], and another extended from ANKK1 exon 8 to DRD2;C957T (p(oihs) = 0.0028), in both samples.
Evidence for the C957T T allele having a role in AD susceptibility at the population level using a case/control comparison was statistically marginal (P = 0.062), but was consistent with the family data results.
The allele frequencies of DRD2 C957T were not significantly different between the CWS and the CWNS; however, the frequency of the TT genotype was significantly higher among the CWS (p = 0.02), which was associated with 2.25-fold susceptibility to stuttering (OR = 2.25, 95% CI = 1.03 to 4.90, p = 0.04).
Research in healthy adults suggests that C957T polymorphism of the dopamine D2 receptor encoding DRD2 and the Taq1A polymorphism of the neighbouring gene ankyrin repeat and kinase domain containing 1 (ANKK1) alter dopaminergic signalling and may influence prefrontally-mediated executive functions.
Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the <i>DRD2</i> TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence.
Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain.
We examined the relation between inhibitory ability (measured by the Stop Signal Task) and polymorphisms of COMT Val158Met and DRD2 C957T in patients with idiopathic PD.