Genetic association of BDNF val66met and GSK-3beta-50T/C polymorphisms with tardive dyskinesia.
OBJECTIVE
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)-3beta are important in neuronal survival, and thus abnormal regulation of BDNF and GSK-3beta 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-3beta 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-3beta-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-3beta 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-3beta 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-3beta gene polymorphisms work in combination, but not individually, in predisposing patients with schizophrenia to TD.
Park
Sung Woo
SW
Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
Lee
Jung Goo
JG
Kong
Bo Geum
BG
Lee
Sun Jung
SJ
Lee
Chan Hong
CH
Kim
Jeong Ik
JI
Kim
Young Hoon
YH
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007723:Korea; D008297:Male; D008715:Methionine / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D014633:Valine / Q000235:genetics
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D014633:Valine