title: Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia.
abstract: Tardive dyskinesia (TD) is a neuroleptic-induced movement disorder. Its pathophysiology is unclear. The most consistent genetic findings have shown an association with the Ser9Gly polymorphism of the DRD3 gene. However, only few polymorphisms within DRD3 has been tested, and a comprehensive examination of DRD3 in TD is still lacking. Further, brain-derived neurotrophic factor (BDNF), a neuronal growth and survival peptide, regulates DRD3 expression and may be involved in the neuronal degeneration observed in TD. In the present study, we investigated 15 tag DRD3 polymorphisms and four tag BDNF polymorphisms for association with TD in our sample of Caucasian schizophrenia patients (N=171). While BDNF markers showed no association, a haplotype containing rs3732782, rs905568, and rs7620754 in the 5' region of DRD3 was associated with TD diagnosis (p[10,000 permutations]=0.007). We also found evidence of interaction between BDNF and DRD3 polymorphisms. Further studies are needed to confirm these findings.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Natalie
authors.initials: N
authors.lastname: Bulgin
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Gwyneth C
authors.initials: GC
authors.lastname: Zai
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D017109:Akathisia, Drug-Induced / Q000209:etiology / Q000235:genetics*; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications; D012694:Serine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050637:Receptors, Dopamine D3; D012694:Serine; D005998:Glycine