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Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients

Published online by Cambridge University Press:  18 April 2024

Hanna Puolakka Open the ORCID record for Hanna Puolakka [Opens in a new window] ,
Anssi Solismaa ,
Leo-Pekka Lyytikäinen ,
Merja Viikki ,
Niko Seppälä ,
Nina Mononen ,
Terho Lehtimäki  and
Olli Kampman Open the ORCID record for Olli Kampman [Opens in a new window]
Hanna Puolakka*
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Anssi Solismaa
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland
Leo-Pekka Lyytikäinen
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Merja Viikki
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, The Wellbeing Services County of Ostrobothnia, Seinäjoki, Finland
Niko Seppälä
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, Satasairaala Hospital, The Satakunta Wellbeing Services County, Pori, Finland
Nina Mononen
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Terho Lehtimäki
Affiliation:
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Olli Kampman
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland Department of Psychiatry, Department of Clinical Sciences (Psychiatry), Faculty of Medicine, University Hospital of Umeå, Umeå University, Umeå, Sweden Department of Clinical Medicine (Psychiatry), Faculty of Medicine, University of Turku, Turku, Finland Department of Psychiatry, The Wellbeing Services County of Ostrobothnia, Vaasa, Finland
*
Corresponding author: H. Puolakka; Email: hannapuolakka97@gmail.com
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Abstract

Background:

Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes.

Methods:

The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients.

Results:

Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029).

Conclusion:

Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Keywords

Adverse effectsclozapinepharmacogeneticssialorrheaxerostomia
Type
Original Article
Information
Acta Neuropsychiatrica , First View , pp. 1 - 6
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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