Premium
Genetic association of BDNF val66met and GSK‐3β‐50T/C polymorphisms with tardive dyskinesia
Author(s) -
Park Sung Woo,
Lee Jung Goo,
Kong Bo Geum,
Lee Sun Jung,
Lee Chan Hong,
Kim Jeong Ik,
Kim Young Hoon
Publication year - 2009
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/j.1440-1819.2009.01976.x
Subject(s) - tardive dyskinesia , dyskinesia , genotype , allele , brain derived neurotrophic factor , medicine , gsk 3 , endocrinology , neurotrophic factors , schizophrenia (object oriented programming) , pathogenesis , allele frequency , genetics , psychology , biology , psychiatry , gene , parkinson's disease , signal transduction , disease , receptor
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.