Genetic association of BDNF val66met and GSK-3β-50T/C polymorphisms with tardive dyskinesia
Article first published online: 27 APR 2009
© 2009 The Authors. Journal compilation © 2009 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences
Volume 63, Issue 4, pages 433–439, August 2009
How to Cite
Park, S. W., Lee, J. G., Kong, B. G., Lee, S. J., Lee, C. H., Kim, J. I. and Kim, Y. H. (2009), Genetic association of BDNF val66met and GSK-3β-50T/C polymorphisms with tardive dyskinesia. Psychiatry and Clinical Neurosciences, 63: 433–439. doi: 10.1111/j.1440-1819.2009.01976.x
- Issue published online: 16 JUL 2009
- Article first published online: 27 APR 2009
- Received 15 November 2007; revised 5 January 2009; accepted 19 February 2009.
- brain-derived neurotrophic factor;
- glycogen synthase kinase-3β;
- tardive dyskinesia
Aims: Neurodegenerative processes may be involved in the pathogenesis of tardive dyskinesia (TD), and a growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in both the antipsychotic effects and the pathogenesis of TD. BDNF and glycogen synthase kinase (GSK)-3β are important in neuronal survival, and thus abnormal regulation of BDNF and GSK-3β may contribute to TD pathophysiology. This study investigated the relationship between two polymorphisms, val66met in the BDNF coding region and -50T/C in the GSK-3β promoter, and susceptibility to TD among a matched sample of patients having schizophrenia with TD (n = 83), patients with schizophrenia without TD (n = 78), and normal control subjects (n = 93).
Methods: All subjects were Korean. The BDNF val66met and GSK-3β-50T/C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses.
Results: Polymerase chain reaction analysis revealed no significant difference in the occurrence of the polymorphisms among the TD, non-TD, and control subjects, but a significant interaction was observed among the groups possessing BDNF val allele in compound genotypes (P = 0.001). We found that the schizophrenic subjects with the C/C GSK-3β genotype, who carry the val allele of the BDNF gene, are expected to have a decreased risk of developing neuroleptic-induced tardive dyskinesia (P < 0.001).
Conclusions: Our results demonstrate that the GSK-3β C/C genotype with the BDNF val allele is associated with patients having schizophrenia without TD. This study also suggests that the BDNF and GSK-3β gene polymorphisms work in combination, but not individually, in predisposing patients with schizophrenia to TD.