Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis

Abstract

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.

Molecular epidemiology of major depressive disorder

“…Brain imaging studies of healthy volunteers have shown that individuals with an A1 allele (C allele of C32806T) of DRD2 have a reduced number of dopamine D2 receptors [134,135]. The DRD3 Ser9Gly genotypes were reported to differ with regard to their dopamine-binding affinity [136]. The most widely studied polymorphism of DRD4 is a 48 bp variable number of tandem repeats (VNTR) which encodes for the third intracytoplasmic loop and contains 2-11 repeats [137].…”

Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant

“…42 Results from the association studies between DRD3 Ser9Gly and SCZ have been inconclusive. Although initial metaanalyses have provided some evidence for a marginal association between the Ser allele, Ser-containing genotypes and Ser9Gly homozygosity with SCZ, [43][44][45] these findings have not been supported by larger, more recent meta-analyses. [46][47][48] These observations, however, do not preclude a variation in DRD3 to be irrelevant for APD response.…”

“…Several lines of evidence suggest a role for D3. Furthermore, an earlier meta-analysis by Jönsson et al (2003) (n ¼ 233) suggested a role for genetic variation in the D3 gene. Relevant to this study, Jönsson et al found the Ser allele of the D3 serine-to-glycine substitution at amino acid position 9 (Ser9Gly) polymorphism to be associated with worse CLZ response compared with the Gly allele.…”

Le récepteur dopaminergique D3: nouvelle cible pour un traitement amélioré de la schizophrénie

“…Il s'agit de la substitution d'une sérine par une glycine (Ser9Gly) qui aurait comme consé-quence une affinité plus importante pour la DA. La majorité de ces études suggère effectivement une association positive entre ce polymorphisme et la schizophrénie, mais de nombreux rapports négatifs ne permettent pas de conclusions définitives [40,41]. Une association éventuelle entre les récep-teurs D 3 , seuls ou en interaction avec d'autres gènes, et la schizophrénie nécessite donc des analyses plus complètes.…”