title: Association between a COMT polymorphism and clinical response to risperidone treatment:  a pharmacogenetic study.
abstract: A total of 130 Chinese schizophrenic patients (45 male, 85 female) were enrolled in the study. Clinical efficacy was determined using Brief Psychiatric Rating Scale (BPRS) scores. We genotyped 10 single-nucleotide polymorphisms (SNPs) of the catechol-O-methyl transferase gene (COMT) in our patients and re-examined them for association with changes in BPRS scores after 8 weeks of risperidone monotherapy. COMT is one of the genes that confer susceptibility to schizophrenia, both because of its role in neurotransmitter metabolism and because of its location in the high-risk schizophrenia-related region 22q11. Recent studies also found that COMT functional polymorphisms influenced individual response to antipsychotic medication. Our aim in this study was to explore the influence of COMT polymorphisms on pharmacological response to risperidone in the Chinese population. Statistical analysis revealed a significant association between an upstream COMT SNP, rs9606186, and scores reduction of BPRS in all patients and in the male subgroup but not in the female subgroup (allele analysis: P=0.055 for all, P=0.012 for male patients; genotype analysis: P=0.046 for all, P=0.020 for male patients, uncorrected, odds ratio=3.95). The COMT gene polymorphism, SNP rs9606186, is associated with risperidone therapy efficiency in the Chinese population. This association exhibited a sexually dimorphic difference, which may shed light on the genetics of COMT and its enzymatic sex-dependent mechanism.
authors.affiliation: Bio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, People's Republic of China.
authors.forename: Qing-Zhu
authors.initials: QZ
authors.lastname: Zhao
authors.forename: Bao-Cheng
authors.initials: BC
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jue
authors.initials: J
authors.lastname: Ji
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Yang
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Wan
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Xu
authors.forename: Guo-Yin
authors.initials: GY
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Guang
authors.initials: G
authors.lastname: He
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D002394:Catechol O-Methyltransferase; D018967:Risperidone