Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia.
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.
Zai
Clement C
CC
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Tiwari
Arun K
AK
De Luca
Vincenzo
V
Müller
Daniel J
DJ
Bulgin
Natalie
N
Hwang
Rudi
R
Zai
Gwyneth C
GC
King
Nicole
N
Voineskos
Aristotle N
AN
Meltzer
Herbert Y
HY
Lieberman
Jeffrey A
JA
Potkin
Steven G
SG
Remington
Gary
G
Kennedy
James L
JL
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
D019208:Brain-Derived Neurotrophic Factor; D050637:Receptors, Dopamine D3; D012694:Serine; D005998:Glycine