title: Histamine H4 receptor polymorphism: a potential predictor of risperidone efficacy.
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 χ(2), 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.
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors: Zhiyun
authors: Z
authors: Wei
authors: Lei
authors: L
authors: Wang
authors: Tao
authors: T
authors: Yu
authors: Yang
authors: Y
authors: Wang
authors: Liya
authors: L
authors: Sun
authors: Ti
authors: T
authors: Wang
authors: Ran
authors: R
authors: Huo
authors: Yang
authors: Y
authors: Li
authors: Xi
authors: X
authors: Wu
authors: Shengying
authors: S
authors: Qin
authors: Yifeng
authors: Y
authors: Xu
authors: Guoyin
authors: G
authors: Feng
authors: Lin
authors: L
authors: He
authors: Qinghe
authors: Q
authors: Xing
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D018967:Risperidone