Association between monoamine oxidase A gene promoter 30 bp repeat polymorphism and tardive dyskinesia in Chinese schizophrenics

BACKGROUND ： The pathophysiology of tardive dyskinesia （TD） is not yet fully understood. With the hypothesis of altered dopaminergic neurotransmission, altered activities of dopamine degrading enzymes such as monoamine oxidase A （MAOA） and their coding genes are supposed to be related to the pathophysiology of TD. OBJECTIVE： To investigate possible association between 30 bp variable number tandem repeat （VNTR） polymorphism in the promoter of MAOA gene and susceptibility, severity of neuroleptic induced TD in Chinese Han people in Guandong Province. DESIGN ： Non-randomization-synchronization controlled study.SETTING： Guangdong Mental Health Institute, Guangdong Provincial People＇s Hospital; Guangzhou Psychiatric Hospital; Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration. PARTICIPANTS： A total of 179 subjects were enrolled in the study. All subjects were sporadic and genetically unrelated Chinese schizophrenic patients who were hospitalizing in Guangzhou Psychiatric Hospital or Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration during January to April 2005. The diagnosis of schizophrenia was made according to the criteria of Diagnostic and Statistic Manual of Mental Disorder-the third edition-revised （DSM-Ⅲ-R）. Among all patients, 88 were diagnosed as with TD and 91 without TD according to the research diagnostic criteria described by Schooler-Kane. Informed consent was obtained from all subjects or their relatives. METHODS ： ① TD seventy was assessed with the AIMS which was a 5-degree rating scale from 0 to 4 （corresponding to none, minimal, mild, moderate and severe, respectively）. The study was approved by the Ethics Committees of the two hospitals and informed consent was obtained from all subjects or their relatives. ② The polymerase chain reaction （PCR） and polyacrylamide gel electrophoresis （PAGE） techniques were used to detect MAOA gene 30 bp VNTR polymorphism in schizophrenic patients with and without TD. ③ The differences in genotype and allele frequencies between two groups were compared with chi-square test and severity of TD rated by Abnormal Involuntary Movement Scale （AIMS） among TD patients with different genotypes or alleles were compared with one way ANOVA test or independent-samples t test. MAIN OUTCOME MEASURES： Demographic and clinical variables including sex, age, duration of illness, cumulative exposure to neuroleptic drugs, times of hospitalization, of all patients; AIMS scores in TD patients; MAOA gene polymorphic allelic and genotypic frequencies in all subjects. RESULTS： All 179 subjects were involved in the final analysis. No one was dropped out in this study.Only 3- and 4-fold repeat alleles were observed in all subjects. Data was stratified and analyzed by gender because MAOA gene was located on the X chromosome. No significant differences were found in genotypic （X^2=2.437, P 〉 0.05） nor allelic （X^2=2.233, P 〉 0.05） frequencies of MAOA gene between patients with TD and without TD in female subjects, and no significant differences in allelic frequencies between male TD and non-TD patients （X^2 =1.750, P 〉 0.05）. And there were no significant differences in mean AIMS scores among female TD patients with different MAOA genotypes （F=1.190, P 〉 0.05） and between male TD patients carrying different alleles （t =0.378, P〉 0.05）. CONCLUSION ： The results do not support any associations between MAOA gene 30 bp VNTR polymorphism and susceptibility nor severity of TD in schizophrenia in Chinese Han people.