Genotype-phenotype analysis of paraoxonase 1 in schizophrenic patients treated with atypical antipsychotics

Abstract

Objective: Recent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants. Methods: We assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of PON1 gene (Q192R, L55M, 108C>T). Results: We found significantly lower (13.3%) AREase activity in schizophrenic patients, along with significantly lower (8.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and 108C>T polymorphisms distributions were similar. Conclusion: We identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.