title: Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients.
abstract: The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years. However, the existence of inconsistent reports makes the role of the DRD3 ser9gly polymorphism in TD development questionable. In rodent studies, the DRD3 expression could be controlled by the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family. In this study, we examined the association between the DRD3 ser9gly and BDNF val66met genetic polymorphisms and TD occurrence in 216 schizophrenic patients (TD/non-TD = 102/114). In addition, we also studied the effects of the DRD3 ser9gly and BDNF val66met genotypes and their gene-gene interaction on the clinical expression of TD in these TD patients. We found that the TD patients who were heterozygous for the BDNF genotypes had significantly higher abnormal involuntary movement scale (AIMS) orofacial scores (corrected p = 0.021, Bonferroni correction), and a trend of higher AIMS total and limb-trunk scores than the combined homozygous analogs. The correlation between the DRD3 ser9gly genotypes and its interaction with the BDNF val66met polymorphism, and the three classes of AIMS scores were not statistically significant. Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence. We concluded that the BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after TD has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary.
authors.affiliation: Department of Psychiatry, Yu-Li Veterans Hospital, Hualien, Taiwan, ROC.
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
authors.forename: Ding-Lieh
authors.initials: DL
authors.lastname: Liao
authors.forename: Jen-Yeu
authors.initials: JY
authors.lastname: Chen
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Wang
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.forename: Shun-Chieh
authors.initials: SC
authors.lastname: Yu
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D013624:Taiwan
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3