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Association between CYP1A2 gene single nucleotide polymorphisms and clinical responses to clozapine in patients with treatment-resistant schizophrenia

Published online by Cambridge University Press:  22 February 2013

Anto P. Rajkumar ,
B. Poonkuzhali ,
Anju Kuruvilla ,
Alok Srivastava ,
Molly Jacob  and
K. S. Jacob
Anto P. Rajkumar*
Affiliation:
Department of Psychiatry, Christian Medical College, Vellore 632002, India Center for Psychiatric Research, Aarhus University Hospital, Risskov-8240, Denmark
B. Poonkuzhali
Affiliation:
Department of Haematology, Christian Medical College, Vellore 632002, India
Anju Kuruvilla
Affiliation:
Department of Psychiatry, Christian Medical College, Vellore 632002, India
Alok Srivastava
Affiliation:
Department of Haematology, Christian Medical College, Vellore 632002, India
Molly Jacob
Affiliation:
Department of Biochemistry, Christian Medical College, Vellore 632002, India
K. S. Jacob
Affiliation:
Department of Psychiatry, Christian Medical College, Vellore 632002, India
*
Dr Anto Praveen Rajkumar Rajamani, Centre for Psychiatric Research, Aarhus University Hospital, 2, Skovagervej, Risskov-8240, Denmark. Tel: +45 7789 3548; Fax: +45 8612 3173; E-mail: antoprajkumar@yahoo.com
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Abstract

Objectives

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).

Conclusion

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.

Keywords

clozapinecytochrome P-450 CYP1A2pharmacogeneticssingle nucleotide polymorphism
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 1 , February 2013 , pp. 2 - 11
Copyright
Scandinavian College of Neuropsychopharmacology 2013

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