Impact of histamine receptors H1 and H3 polymorphisms on antipsychotic-induced weight gain

Arun K. Tiwari, Danning Zhang, Jennie G. Pouget, Clement C. Zai, Nabilah I. Chowdhury, Eva J. Brandl, Li Qin, Natalie Freeman, Jeffrey A. Lieberman, Herbert Y. Meltzer, James L. Kennedy, Daniel J. Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objectives: A positive correlation between antipsychotic-induced weight gain (AIWG) and the antagonist effect of antipsychotic drugs at the histamine H1 receptor (HRH1) as well as the agonist effect at the histamine H3 receptor (HRH3) in the brain has been consistently demonstrated. We investigated the potential impact of single-nucleotide polymorphisms (SNPs) in HRH1 and HRH3 genes on AIWG. Methods: We analysed 40 tagSNPs in HRH1 (n = 34) and HRH3 (n = 6) in schizophrenia/schizoaffective disorder patients (n = 193) primarily treated with clozapine or olanzapine for up to 14 weeks. Linear regression was used to evaluate the association between SNPs and AIWG, with baseline weight and treatment duration as covariates. Results: In HRH1, a nominal association of rs7639145 with AIWG was observed in patients of European ancestry treated with either clozapine or olanzapine (P= 0.043; β = 1.658; n = 77). We observed nominal association for two HRH1 SNPs rs346074 (P = 0.002; β = –5.024) and rs13064530 (P= 0.004; β = –5.158) in patients of African ancestry treated with either clozapine or olanzapine (n = 37). However, the above associations are not significant after correcting for multiple testing. In HRH3, we did not observe association in either ancestry. Conclusions: The current study suggests that SNPs in HRH1 and HRH3 may not have a major role in AIWG.

Original languageEnglish (US)
Pages (from-to)S97-S105
JournalWorld Journal of Biological Psychiatry
Volume19
Issue numbersup3
DOIs
StatePublished - Nov 15 2018

Funding

DJM has received a CIHR operating grant (MOP 89853 & MOP 142192), a NARSAD Young Investigator Award, a CIHR Michael Smith New Investigator Salary Prise for Research in Schizophrenia, an Early Researcher Award from the Ministry of Research and Innovation, Ontario, and an OMHF New Investigator Fellowship. JLK is a recipient of a CIHR operating grant. NIC is a recipient of OMHF Research Studentship. JGP is supported by Brain Canada through the Canada Brain Research Fund, a public-private partnership established by the Government of Canada. Canadian Institute of Health Research Operating grants [MOP 89853, MOP 142192]. DJM has received a CIHR operating grant (MOP 89853 & MOP 142192), a NARSAD Young Investigator Award, a CIHR Michael Smith New Investigator Salary Prise for Research in Schizophrenia, an Early Researcher Award from the Ministry of Research and Innovation, Ontario, and an OMHF New Investigator Fellowship. JLK is a recipient of a CIHR operating grant. NIC is a recipient of OMHF Research Studentship. JGP is supported by Brain Canada through the Canada Brain Research Fund, a public-private partnership established by the Government of Canada.

Keywords

  • SNP
  • Schizophrenia
  • clozapine
  • histamine receptor
  • weight gain

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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