Histamine H4 Receptor Polymorphism: A Potential Predictor of Risperidone Efficacy : Journal of Clinical Psychopharmacology

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Histamine H4 Receptor Polymorphism

A Potential Predictor of Risperidone Efficacy

Wei, Zhiyun BS*†; Wang, Lei PhD*‡; Yu, Tao PhD*†; Wang, Yang PhD*†; Sun, Liya MS*†; Wang, Ti BS*†; Huo, Ran MS*†; Li, Yang MS*†; Wu, Xi MS*†; Qin, Shengying PhD*†; Xu, Yifeng MD§; Feng, Guoyin MD§; He, Lin PhD*†‡; Xing, Qinghe PhD*‡

Author Information

From the *Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University; †Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences; ‡Children’s Hospitaland Institutes of Biomedical Sciences, Fudan University; and §Shanghai Institute of Mental Health, Shanghai, PR China.

Received August 17, 2011; accepted after revision July 11, 2012.

Reprints: Lin He, PhD, and Qinghe Xing, PhD, Bio-X Institutes, Shanghai Jiao Tong University, 1954 Hua Shan Rd, Shanghai 200030, China; or Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China (e-mail: [email protected] and [email protected]).

This work was supported by the National Natural Science Foundation of China (No. 30971582; 90919049), the 973 Program (2010CB529600, 2009CB825606), the 863 Program (2009AA022701), the Shanghai Municipal Commission of Science, and Technology Program (09DJ1400601), the National Key Project for Investigational New Drug 2008ZX09312-003, and the Shanghai Leading Academic Discipline Project (B205).

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com).

Journal of Clinical Psychopharmacology 33(2):p 221-225, April 2013. | DOI: 10.1097/JCP.0b013e318283963b

Abstract

Histamine interacts with histamine H4 receptor (HRH4) to impact antipsychotic response. Pharmacogenetic information about this receptor could therefore be useful in developing individualized therapy. The aim of this investigation was to clarify whether polymorphisms at human HRH4 gene alter risperidone efficacy. We genotyped 5 tag-single nucleotide polymorphisms of the HRH4 gene and analyzed their association with the reduction in Positive and Negative Syndrome Scale (PANSS) scores in a group of 113 Chinese Han patients with schizophrenia who were following an 8-week period of risperidone monotherapy. Using χ2, analysis of variance, haplotype, and receiver operating characteristics analysis, we found that HRH4 common variant rs4483927 is significantly associated with risperidone efficacy and that its TT genotype predicts poor therapeutic response both on the positive, negative, and general subscales and on the total scale of PANSS scores (P = 0.017, 0.019, 0.021, and 0.002, respectively, in analysis of variance). Our results provide the first evidence that an HRH4 polymorphism may be a molecular marker for the prediction of risperidone efficacy and suggest novel pharmacologic links between HRH4 gene and treatment of schizophrenia.

© 2013 by Lippincott Williams & Wilkins.

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