Abstract
BackgroundCytochrome 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.MethodsA 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.ResultsThe 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).ConclusionsThis 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.
Highlights
Cytochrome P450 1A2 gene (CYP1A2) polymorphisms have been suggested to be associated with increased side effects to antipsychotics
An increased tardive dyskinesia severity was observed in patients with the A allele of the CYP1A2*1C polymorphism and in another study with CYP1A2 (C→A) [9,10], while the CYP1A2 −163C > A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures [11]
To the best of our knowledge, only one previous study has reported a possible association between the −1545C > T polymorphism and the side effects of antipsychotics; in this analysis, 1545C > T was initially associated with tardive dyskinesia, but, after multiple corrections, this finding was shown to be insignificant [14]
Summary
Cytochrome P450 1A2 gene (CYP1A2) polymorphisms have been suggested to be associated with increased side effects to antipsychotics. 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. An increased tardive dyskinesia severity was observed in patients with the A allele of the CYP1A2*1C polymorphism and in another study with CYP1A2 (C→A) [9,10], while the CYP1A2 −163C > A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures [11]. To the best of our knowledge, only one previous study has reported a possible association between the −1545C > T (rs2470890) polymorphism and the side effects of antipsychotics; in this analysis, 1545C > T was initially associated with tardive dyskinesia, but, after multiple corrections, this finding was shown to be insignificant [14]
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