Genetic Polymorphisms Associated With Constipation and Anticholinergic Symptoms in Patients Receiving Clozapine.
J Clin Psychopharmacol
; 38(3): 193-199, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29620694
ABSTRACT
BACKGROUND:
Clozapine impairs gastrointestinal motility owing to its anticholinergic and antiserotonergic properties. This commonly leads to constipation and potentially to more severe complications such as bowel obstruction and ischemia. The aim of this study was to determine whether genetic variations in the genes encoding muscarinic and serotonergic receptors (CHRM2, CHRM3, HTR2, HTR3, HTR4, and HTR7) explain the variations in incidence of constipation and anticholinergic symptoms during clozapine treatment. Genes associated with opiate-induced constipation were also included in this analysis (TPH1, OPRM1, ABCB1, and COMT). PROCEDURES Blood samples from 176 clozapine-treated, Finnish, white patients with schizophrenia were genotyped. Constipation and anticholinergic symptoms were rated using the Liverpool University Neuroleptic Side Effect Rating Scale self-report questionnaire. In total, 192 single-nucleotide polymorphisms (SNPs) were detected and grouped to formulate a weighted genetic-risk score (GRS).RESULTS:
No significant associations between individual SNPs or GRSs and constipation or laxative use were observed. A GRS of 19 SNPs in CHRM2, CHRM3, HTR3C, HTR7, ABCB1, OPRM1, and TPH1 was associated with anticholinergic symptoms in a generalized linear univariate model, with body mass index, clozapine monotherapy, and GRS as explaining variables (permuted P = 0.014). Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002).CONCLUSIONS:
Two GRSs are able to predict the risk of anticholinergic symptoms in patients receiving clozapine and possibly an increased risk of gastrointestinal hypomotility.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Antipsicóticos
/
Clozapina
/
Estreñimiento
/
Motilidad Gastrointestinal
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Clin Psychopharmacol
Año:
2018
Tipo del documento:
Article