ABSTRACT
OBJECTIVE: To further evaluate the controversial putative association between a Ser9Gly variant in the first exon of the dopamine D3 receptor gene (DRD3) and schizophrenia. METHODS: Swedish patients with schizophrenia ( n=156) and control subjects ( n=463) were assessed for the DRD3 Ser9Gly variant. Meta-analyses including previous and the present Swedish case-control results were performed. RESULTS: No significant difference between the Swedish patients and controls were found, but there was an association between DRD3 Ser9Gly Ser/Ser and homozygous genotypes and response to anti-psychotic drugs. This finding was supported by an incomplete meta-analysis. In a meta-analysis of all case-control studies comprising 8761 subjects the association between DRD3 Ser9Gly homozygosity and schizophrenia ( =4.96, degree of freedom=1, p <0.05, odds ratio=1.10, 95% confidence interval=1.01-1.20) persisted. However, the previously proposed association between the Ser/Ser genotype and schizophrenia was not significant (chi2 =2.71, degree of freedom=1, p>0.05, odds ratio=1.08, 95% confidence interval=0.99-1.17). CONCLUSIONS: Whereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia. Reasons for the discrepancies between prior studies are discussed.
Subject(s)
Amino Acid Substitution , Genetic Variation , Receptors, Dopamine D2/genetics , Schizophrenia/genetics , Case-Control Studies , Glycine , Homozygote , Humans , Receptors, Dopamine D3 , Reference Values , Serine , SwedenABSTRACT
Dopamine receptor gene variation has been hypothesized to influence personality traits characterized by novelty seeking and related traits. We analyzed a dopamine D(3) receptor gene (DRD3) variant in a Swedish population (n = 373) investigated with one or more of several personality questionnaires. No significant relationships were found between DRD3 genotypes and any of the 15 Karolinska Scales of Personality (KSP) and five Health-relevant Personality 5 factor inventory (HP5i) scales. The DRD3 variant was associated with some scales related to novelty seeking: the Swedish universities Scales of Personality (SSP) Adventure Seeking and the revised NEO personality inventory (NEO-PI-R) Fantasy (O1) and Order (C2) scales. There were also associations with the Temperament and Character Inventory (TCI) Cooperativeness and Compassion (C4) scales. After correction for multiple testing, however, no significant difference remained. We conclude that the investigated DRD3 polymorphism does not have a major impact on personality in the investigated population.
