title: CYP1A2 polymorphism -1545C > T (rs2470890) is associated with increased side effects to clozapine.
abstract: BACKGROUND
  Cytochrome P450 1A2 gene (CYP1A2) polymorphisms have been suggested to be associated with increased side effects to antipsychotics. However, studies on this are scarce and have been conducted with either various antipsychotics or only in small samples of patients receiving clozapine. The aim of the present study was to test for an association between the CYP1A2 -1545C > T (rs2470890) polymorphism and side effects in a larger sample of patients during long-term clozapine treatment.
  
  
  METHODS
  A total of 237 patients receiving clozapine treatment completed the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) assessing clozapine-induced side effects. Of these patients, 180 completed the questionnaire satisfactorily, agreed to provide a blood sample, and were successfully genotyped for the polymorphism.
  
  
  RESULTS
  The TT genotype of CYP1A2 polymorphism -1545C > T (rs2470890) was associated with significantly more severe side effects during clozapine treatment (p = 0.011). In a subanalysis, all seven types of side effects (sympathicotonia-tension; depression-anxiety; sedation; orthostatic hypotension; dermal side effects; urinary side effects; and sexual side effects) appeared numerically (but insignificantly) more severely among TT carriers. In addition, use of mood stabilizers was more common among patients with the TT genotype (OR = 2.63, p = 0.004).
  
  
  CONCLUSIONS
  This study has identified an association between the CYP1A2 polymorphism -1545C > T (rs2470890) and the occurrence of more severe clozapine side effects. However, these results should be regarded as tentative and more studies of larger sample sizes will be required to confirm the result.
authors.affiliation: University of Tampere, Medical School, University of Tampere, Tampere 33014, Finland. merja.viikki@gmail.com.
authors.forename: Merja
authors.initials: M
authors.lastname: Viikki
authors.forename: Olli
authors.initials: O
authors.lastname: Kampman
authors.forename: Niko
authors.initials: N
authors.lastname: Seppälä
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; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D019388:Cytochrome P-450 CYP1A2; D003024:Clozapine