title: Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment.
abstract: 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.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Department of Psychiatry, Seinäjoki Hospital District, Seinäjoki, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Solismaa
authors.forename: Olli
authors.initials: O
authors.lastname: Kampman
authors.forename: Niko
authors.initials: N
authors.lastname: Seppälä
authors.forename: Merja
authors.initials: M
authors.lastname: Viikki
authors.forename: Kari-Matti
authors.initials: KM
authors.lastname: Mäkelä
authors.forename: Nina
authors.initials: N
authors.lastname: Mononen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Esa
authors.initials: E
authors.lastname: Leinonen
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056926:CLOCK Proteins / Q000235:genetics; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012798:Sialorrhea / Q000139:chemically induced* / Q000235:genetics*
chemical_list: C547768:ADRA2A protein, human; D014150:Antipsychotic Agents; C086088:CHRM1 protein, human; C000595896:CHRM3 protein, human; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D018341:Receptors, Adrenergic, alpha-2; D011976:Receptors, Muscarinic; D056926:CLOCK Proteins; C538943:CLOCK protein, human; D003024:Clozapine
keywords: ADRA2A; clozapine; drug toxicity; polymorphism; sialorrhea; single nucleotide