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

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Title: Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication.
Authors: Vehof, Jelle, Risselada, Arne, Hadithy, Asmar, Burger, Huibert, Snieder, Harold, Wilffert, Bob, Arends, Johan, Wunderink, Lex, Knegtering, Henrikus, Wiersma, Durk, Cohen, Dan, Mulder, Hans, Bruggeman, Richard
Source: Psychopharmacology. Jul2011, Vol. 216 Issue 2, p257-265. 9p. 3 Charts, 1 Graph.
Subjects: Human genetic variation, Histamine, Muscarinic receptors, Body mass index, Antipsychotic agents, Schizophrenia, Muscarine, Weight gain, Pharmacogenomics, Genetic polymorphisms
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication.
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  Data: <searchLink fieldCode="AR" term="%22Vehof%2C+Jelle%22">Vehof, Jelle</searchLink><br /><searchLink fieldCode="AR" term="%22Risselada%2C+Arne%22">Risselada, Arne</searchLink><br /><searchLink fieldCode="AR" term="%22Hadithy%2C+Asmar%22">Hadithy, Asmar</searchLink><br /><searchLink fieldCode="AR" term="%22Burger%2C+Huibert%22">Burger, Huibert</searchLink><br /><searchLink fieldCode="AR" term="%22Snieder%2C+Harold%22">Snieder, Harold</searchLink><br /><searchLink fieldCode="AR" term="%22Wilffert%2C+Bob%22">Wilffert, Bob</searchLink><br /><searchLink fieldCode="AR" term="%22Arends%2C+Johan%22">Arends, Johan</searchLink><br /><searchLink fieldCode="AR" term="%22Wunderink%2C+Lex%22">Wunderink, Lex</searchLink><br /><searchLink fieldCode="AR" term="%22Knegtering%2C+Henrikus%22">Knegtering, Henrikus</searchLink><br /><searchLink fieldCode="AR" term="%22Wiersma%2C+Durk%22">Wiersma, Durk</searchLink><br /><searchLink fieldCode="AR" term="%22Cohen%2C+Dan%22">Cohen, Dan</searchLink><br /><searchLink fieldCode="AR" term="%22Mulder%2C+Hans%22">Mulder, Hans</searchLink><br /><searchLink fieldCode="AR" term="%22Bruggeman%2C+Richard%22">Bruggeman, Richard</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Jul2011, Vol. 216 Issue 2, p257-265. 9p. 3 Charts, 1 Graph.
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  Data: <searchLink fieldCode="DE" term="%22Human+genetic+variation%22">Human genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Histamine%22">Histamine</searchLink><br /><searchLink fieldCode="DE" term="%22Muscarinic+receptors%22">Muscarinic receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Body+mass+index%22">Body mass index</searchLink><br /><searchLink fieldCode="DE" term="%22Antipsychotic+agents%22">Antipsychotic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Schizophrenia%22">Schizophrenia</searchLink><br /><searchLink fieldCode="DE" term="%22Muscarine%22">Muscarine</searchLink><br /><searchLink fieldCode="DE" term="%22Weight+gain%22">Weight gain</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacogenomics%22">Pharmacogenomics</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink>
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00213-011-2211-x
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        Text: English
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      – SubjectFull: Human genetic variation
        Type: general
      – SubjectFull: Histamine
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      – SubjectFull: Muscarinic receptors
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      – SubjectFull: Body mass index
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      – SubjectFull: Antipsychotic agents
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