Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis.
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.
Jönsson
Erik G
EG
Department of Clinical Neuroscience, HUBIN Project, Karolinska Institutet, Stockholm, Sweden. erikj@ks.se
Flyckt
Lena
L
Burgert
Edgar
E
Crocq
Marc-Antoine
MA
Forslund
Kaj
K
Mattila-Evenden
Marja
M
Rylander
Gunnar
G
Asberg
Marie
M
Nimgaonkar
Vishwajit L
VL
Edman
Gunnar
G
Bjerkenstedt
Lars
L
Wiesel
Frits-Axel
FA
Sedvall
Göran C
GC
D019943:Amino Acid Substitution; D016022:Case-Control Studies; D014644:Genetic Variation; D005998:Glycine; D006720:Homozygote; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*; D012694:Serine; D013548:Sweden
C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012694:Serine; D005998:Glycine