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Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication

RATIONALE: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. OBJECTIVES: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor...

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Autores principales: Vehof, Jelle, Risselada, Arne J., Al Hadithy, Asmar F. Y., Burger, Huibert, Snieder, Harold, Wilffert, Bob, Arends, Johan, Wunderink, Lex, Knegtering, Henrikus, Wiersma, Durk, Cohen, Dan, Mulder, Hans, Bruggeman, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121946/
https://www.ncbi.nlm.nih.gov/pubmed/21336576
http://dx.doi.org/10.1007/s00213-011-2211-x
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author Vehof, Jelle
Risselada, Arne J.
Al Hadithy, Asmar F. Y.
Burger, Huibert
Snieder, Harold
Wilffert, Bob
Arends, Johan
Wunderink, Lex
Knegtering, Henrikus
Wiersma, Durk
Cohen, Dan
Mulder, Hans
Bruggeman, Richard
author_facet Vehof, Jelle
Risselada, Arne J.
Al Hadithy, Asmar F. Y.
Burger, Huibert
Snieder, Harold
Wilffert, Bob
Arends, Johan
Wunderink, Lex
Knegtering, Henrikus
Wiersma, Durk
Cohen, Dan
Mulder, Hans
Bruggeman, Richard
author_sort Vehof, Jelle
collection PubMed
description RATIONALE: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. OBJECTIVES: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). METHODS: We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. RESULTS: A significant association of interaction between haplotype rs346074–rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. CONCLUSIONS: This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-011-2211-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-31219462011-07-14 Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication Vehof, Jelle Risselada, Arne J. Al Hadithy, Asmar F. Y. Burger, Huibert Snieder, Harold Wilffert, Bob Arends, Johan Wunderink, Lex Knegtering, Henrikus Wiersma, Durk Cohen, Dan Mulder, Hans Bruggeman, Richard Psychopharmacology (Berl) Original Investigation RATIONALE: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. OBJECTIVES: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). METHODS: We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. RESULTS: A significant association of interaction between haplotype rs346074–rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. CONCLUSIONS: This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-011-2211-x) contains supplementary material, which is available to authorized users. Springer-Verlag 2011-02-19 2011 /pmc/articles/PMC3121946/ /pubmed/21336576 http://dx.doi.org/10.1007/s00213-011-2211-x Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Investigation
Vehof, Jelle
Risselada, Arne J.
Al Hadithy, Asmar F. Y.
Burger, Huibert
Snieder, Harold
Wilffert, Bob
Arends, Johan
Wunderink, Lex
Knegtering, Henrikus
Wiersma, Durk
Cohen, Dan
Mulder, Hans
Bruggeman, Richard
Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title_full Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title_fullStr Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title_full_unstemmed Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title_short Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication
title_sort association of genetic variants of the histamine h1 and muscarinic m3 receptors with bmi and hba1c values in patients on antipsychotic medication
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121946/
https://www.ncbi.nlm.nih.gov/pubmed/21336576
http://dx.doi.org/10.1007/s00213-011-2211-x
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