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

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.

Keywords:

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

Acknowledgements

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.

Disclosure statement

AKT/DZ/JP/EJB/CCZ//NIC/NF/DJM report no competing interests. HYM has received grants or is or was a consultant to: Abbott Labs, ACADIA, Alkemes, Bristol Myers Squibb, DaiNippon Sumitomo, Eli Lilly, EnVivo, Janssen, Otsuka, Pfizer, Roche, Sunovion and BiolineRx. HYM is a shareholder of ACADIA and Glaxo Smith Kline. In the past three years JAL reports having received research funding or is a member of the advisory board of Allon, Alkermes Bioline, GlaxoSmithKline Intracellular Therapies, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Psychogenics, F. Hoffmann-La Roche LTD, Sepracor (Sunovion) and Targacept. JAL receive no direct financial compensation or salary support for participation in these researches, consulting, or advisory board activities. JLK has been a consultant to GSK, Sanofi-Aventis, and Dainippon-Sumitomo.

Additional information

Funding

Canadian Institute of Health Research Operating grants [MOP 89853, MOP 142192].