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




Puolakka, Hanna; Solismaa, Anssi; Lyytikäinen, Leo-Pekka; Viikki, Merja; Seppälä, Niko; Mononen, Nina; Lehtimäki, Terho; Kampman, Olli

PublisherWiley-Blackwell

2024

Acta Neuropsychiatrica

Acta neuropsychiatrica

Acta Neuropsychiatr

36

4

218

223

0924-2708

1601-5215

DOIhttps://doi.org/10.1017/neu.2024.9

https://doi.org/10.1017/neu.2024.9

https://research.utu.fi/converis/portal/detail/Publication/387742881



Objective: 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.


Last updated on 2024-26-11 at 14:24