title: A pharmacogenetic study of risperidone on histamine H3 receptor gene (HRH3) in Chinese Han schizophrenia patients.
abstract: Evidence suggests that the human histamine H3 receptor (HRH3) may be involved in the pharmacodynamics of risperidone and influence clinical efficacy. More information on the pharmacogenetics of this receptor may therefore be useful in developing individualized therapy. However, to our knowledge, no study has been reported in this area. The aim of this investigation was to clarify whether H3 receptor polymorphism could affect risperidone efficacy. We genotyped tag single nucleotide polymorphisms (SNPs) of the HRH3 gene (rs3787429 and rs3787430) and analyzed their association with the reduction of Brief Psychiatric Rating Scale (BPRS) score in Chinese Han schizophrenia patients (N = 129), following an eight-week period of risperidone monotherapy. The confounding effects of non-genetic factors were estimated, and then the significant one was included as the covariate for adjustment in statistical analysis. Baseline symptom score was the only significant confounding effect and thus the covariate. After adjustment, significant association of HRH3 with antipsychotic efficacy was detected (for rs3787429, p = 0.013, 0.087 after 4 weeks and 8 weeks of treatment, respectively; for rs3787430, p = 0.024, 0.010 after 4 weeks and 8 weeks of treatment, respectively) and stood up to conservative Bonferroni correction. Our results demonstrate that polymorphism of the HRH3 gene may be a potential genetic marker for predicting the therapeutic effect of risperidone, and suggest novel pharmacological links between HRH3 and risperidone. Further studies with larger samples and different ethnic populations are warranted to confirm our results.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Jiekun
authors.initials: J
authors.lastname: Xuan
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Baocheng
authors.initials: B
authors.lastname: Liu
authors.forename: Liyan
authors.initials: L
authors.lastname: Shao
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Ti
authors.initials: T
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D010054:Brief Psychiatric Rating Scale; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D018100:Receptors, Histamine H3 / Q000235:genetics*; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D018100:Receptors, Histamine H3; D018967:Risperidone