The C/C genotype of the C957T polymorphism of the dopamine D2 receptor is associated with schizophrenia

Abstract

The T allele of the human dopamine D2 receptor (DRD2) gene C957T polymorphism is associated with reduced mRNA translation and stability. This results in decreased dopamine induced DRD2 upregulation and decreased in vivo D2 dopamine binding. Conversely, the C allele of the C957T polymorphism is not associated with such changes in mRNA leading to increased DRD2 expression. PET and postmortem binding studies show that schizophrenia is often associated with increased DRD2 availability. We report that on the basis of comparing the frequencies of the C/C and T/T genotypes of 153 patients with schizophrenia and 148 controls that schizophrenia is associated with the C/C genotype. The C957T shows a population attributable risk for schizophrenia of 24% and an attributable risk in those with schizophrenia of 42%. Increased expression of D2 receptors associated with the C allele is likely to be important in the underlying pathophysiology of at least some forms of schizophrenia. Enhanced understanding of schizophrenia afforded by this finding may lead to advances in treatment and prevention.

Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

“…The SNP remained significantly associated with schizophrenia after the adjustment for multiple testing, according to strict Bonferroni's correction. These data, together with the negligible discrepancies of the allele and genotype frequencies with previous studies in Caucasian populations: Northern European populations living in Australia, Spain, Finland and Russia, [15][16][17][18] support the association of DRD2 with schizophrenia.…”

“…2, 35 Our results in the Bulgarian sample group (Table 2) are consistent with the previous reports by other researchers on the positive association between the synonymous C957T (rs6277) polymorphism and schizophrenia, in different Caucasian populations. [15][16][17][18] In our study, the G allele (allele 2), which corresponds to the C allele in the single nucleotide polymorphism database (dbSNP) and the literature, was identified as the risk allele. After the initial study by Lawford et al, 17 reporting association of rs6277 in the Australian (Caucasian) population, three subsequent studies confirmed significantly higher frequencies of the C allele and the C/C genotype in patients with schizophrenia who were of European descent (in the Finnish, 15 Spanish 16 and Russian 18 populations).…”

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

“…The polymorphism examined by the restriction enzyme NcoI is a common synonymous cytosine to thymine transition at position 957 that has been associated previously with susceptibility to migraine and schizophrenia. 12,30,31 Interestingly, this polymorphism has been reported to have an endocrine correlate. 32 In fact, a recent study carried out on a cohort of subjects from the Sweden National Population Registry reported a high prevalence of 957T genotype in subjects with high systolic and diastolic blood pressure.…”

Association Studies of DRD2 and COMT Gene Polymorphisms with Risperidone-induced Amenorrhea in Female Schizophrenia Patients

“…The rs6277 locus changes the stability and translation level of DRD2 mRNA and alters the expression of DRD2 in dopamine channel [20]. Rs6277 had association with plasma prolactin increasing and schizophrenia in the study of different populations, which is also one of susceptible locus in Chinese Han population schizophrenia patients [21][22][23]. A DRD2 haplotype (-141delC and TaqIA) tended to correlate with better clinical performance of risperidone in Japanese schizophrenia patients [24].…”