Association between genetic variation in CYP1A2 and UGT1A4 and the occurrence of metabolic disorders in patients using clozapine and olanzapine

OBJECTIVE: To investigate the association between genetic polymorphisms in enzymes involved in the metabolism of clozapine and olanzapine and the occurrence of metabolic disorders in psychiatric patients using these antipsychotics. CYP1A2 is the main enzyme involved in the metabolism of clozapine. For olanzapine both CYP1A2 and UGT1A4 play a major role in its metabolism. Both enzymes are known to be polymorphic and can therefore influence exposure to these drugs, which may lead to interindividual differences in the occurrence of metabolic side effects. DESIGN: Observational, cross-sectional study. METHODS: 72 Adult patients using clozapine and 94 adult patients using olanzapine were included in the study. Research data, e.g. age, gender, medication data and data on physical well-being, were obtained from an anonymous database. Genetic data on CYP1A2*1F, CYP1A2*1C and UGT1A4*3B were obtained by genotyping samples of included subjects using validated TaqMan and RFLP-PCR assays. The occurrence of metabolic syndrome was the primary endpoint of this study, individual metabolic disorders were the secondary endpoints. Associations between metabolic disorders and polymorphisms were tested by regression analysis. P < 0.05 was regarded as significant. RESULTS: No association was found between polymorphisms in CYP1A2 or UGT1A4 and the occurrence of metabolic syndrome in patients using clozapine or olanzapine. For the secondary outcome measures, associations were found for the CYP1A2*1F allele and glucose and HDL cholesterol levels. CONCLUSION: Genetic variation in CYP1A2 and UGT1A4 is not associated with the occurrence of metabolic syndrome in patients using clozapine or olanzapine.