title: Association between CYP1A2 gene single nucleotide polymorphisms and clinical responses to clozapine in patients with treatment-resistant schizophrenia.
abstract: OBJECTIVE
  Despite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role of CYP1A2 gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS.
  
  
  METHODS
  We evaluated four single nucleotide polymorphisms (SNP) in the CYP1A2 gene, clinical responses and serum clozapine levels in 101 consecutive patients with TRS on stable doses of clozapine. We defined clozapine response a priori and investigated allelic and genotypic associations. We assessed the socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition and disability of the participants, using standard assessment schedules for appropriate multivariate analyses.
  
  
  RESULTS
  Our results revealed that CYP1A2 gene SNP (*1C, *1D, *1E and *1F) were not associated with clozapine treatment response, adverse effects, serum clozapine levels or with disability (p values > 0.10).
  
  
  CONCLUSIONS
  As CYP1A2 gene SNP do not help to predict the clinical response to clozapine, routine screening for them prior to start clozapine is currently unwarranted. We suggest future longitudinal genome-wide association studies investigating clinical and pharmacogenetic variables together.
authors.affiliation: 1 Department of Psychiatry, Christian Medical College, Vellore 632002, India.
authors.forename: Anto P
authors.initials: AP
authors.lastname: Rajkumar
authors.affiliation: 3 Department of Haematology, Christian Medical College, Vellore 632002, India.
authors.forename: B
authors.initials: B
authors.lastname: Poonkuzhali
authors.affiliation: 1 Department of Psychiatry, Christian Medical College, Vellore 632002, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Kuruvilla
authors.affiliation: 3 Department of Haematology, Christian Medical College, Vellore 632002, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: 4 Department of Biochemistry, Christian Medical College, Vellore 632002, India.
authors.forename: Molly
authors.initials: M
authors.lastname: Jacob
authors.affiliation: 1 Department of Psychiatry, Christian Medical College, Vellore 632002, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Jacob