Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment.

Solismaa, Anssi; Kampman, Olli; Seppälä, Niko; Viikki, Merja; Mäkelä, Kari‐Matti; Mononen, Nina; Lehtimäki, Terho; Leinonen, Esa

Objective Clozapine-induced sialorrhea (CIS) is a common, inconvenient and socially stigmatizing adverse effect. The pathophysiology of CIS may be related to the effect of clozapine on the muscarinic and adrenergic receptors as well as the disruption of the circadian rhythms. The aim of this study was to find out if polymorphisms in muscarinic M1 and M3 receptor genes ( CHRM1 and CHRM3), adrenoceptor alpha 2A gene ( ADRA2A) or clock circadian regulator gene ( CLOCK) are associated with CIS. Methods Two hundred and thirty-seven clozapine-treated Finnish schizophrenia patients were genotyped for CHRM1, CHRM3, CLOCK and ADRA2A polymorphisms, and their salivary dysfunction was assessed with two questions. Twenty-six of these patients had previously been on medication to treat CIS. Comparisons of the genotypes between patients with excessive versus non-excessive salivation were analysed. Genotype distributions between patients and control group and haplotypes were also studied. Results CHRM1, CHRM3 and CLOCK polymorphisms and haplotypes were not associated with CIS. ADRA2A (rs1800544) genotype was associated with CIS ( p = 0.029). In patients with CIS, CC genotype ( n = 103) was more common than in G-allele carriers ( n = 79) ( p = 0.013, OR 2.13, 95% CI: 1.17-3.88). No differences were found in the distributions of genotypes between patients and controls. Conclusions ADRA2A genotype was associated with CIS. Copyright © 2014 John Wiley & Sons, Ltd.

SCHIZOPHRENIA; DROOLING; CLOZAPINE; ADRENERGIC receptors; GENETIC polymorphism research

Human Psychopharmacology: Clinical & Experimental, 2014, Vol 29, Issue 4, p336

0885-6222

Academic Journal

10.1002/hup.2408