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Association between a COMT polymorphism and clinical response to risperidone treatment: a pharmacogenetic study

Zhao, Qing-Zhua,b,c; Liu, Bao-Chenga,b,c; Zhang, Jinga,b,c; Wang, Leia,b,c; Li, Xing-Wanga,b,c; Wang, Yanga,b,c; Ji, Juea,b,c; Yang, Feng-Pinga,b,c; Wan, Chun-Linga,b,c; Xu, Yi-Fengd; Feng, Guo-Yind; He, Lina,b,c; He, Guanga,b,c

doi: 10.1097/YPG.0b013e328358629a
Brief Reports

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.

aBio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University

bInstitutes of Biomedical Sciences, Fudan University

cInstitute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences

dShanghai Institute of Mental Health, Shanghai, People’s Republic of China

Qing-zhu Zhao and Bao-cheng Liu contributed equally to the writing of this article.

Correspondence to He Guang, Bio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai JiaoTong University, 1954 Huashan Road, Shanghai 200030, People’s Republic of China Tel: +86 21 6293 2779; fax: +86 21 6282 2491; e-mail:

Received April 7, 2011

Accepted February 27, 2012

© 2012 Lippincott Williams & Wilkins, Inc.