engleski

Metabolic abnormalities among female patients with schizophrenia following treatment with second generation antipsychotics are associated with ABCB1 genetic polymorphisms

Background. Second generation antipsychotic (SGAs) drugs have brought significant progress in treatment of schizophrenia. However, among patients who respond to treatment well, there is a significant number of those who develop metabolic syndrome (about 50%). Metabolic syndrome is associated with high cerebro and cardiovascular risks and therefore higher morbididy and mortality. Still, obvious interindividual differences in responses to SGAs point out that genetic factor may be relevant. MDR1/ABCB1 gene codes for P-glycoprotein (P-gp), the transmembrane efflux transporter.We investigated the relationships between functional genetic variants of MDR1/ABCB1 and SGA-induced metabolic disturbances and treatment response to olanzapine and risperidone among female schizophrenic patients. Methods. We recruited 121 female schizophrenic patients following DSM-IV criteria, who were acutely psychotic and treated with olanzapine or risperidone for up to 3 months. Metabolic syndrome developement (which included assessment of the increase of fasting glucose levels in blood, fasting total cholesterol, LDL, HDL and triglyceride levels, blood preassure and waist and hip circumferences) was assessed. Genomic DNA was isolated from a whole blood sample of patients and exon 21 G2677T/A and exon 26 C3435T genetic variants of ABCB1 were identified by Real time PCR method in Roche LightCycler Fast Start DNA Master plus HybProbe master mix. Results. We found significant associations between ABCB1 exon 21 G2677T/A and exon 26 C3435T genotypes and metabolic changes, with T allele of both loci being associated with significantly greater increase of waist and hip circumferences and greatest increase in fasting glucose level in blood. Furthermore, we found significant associations between 2677T allele and TT genotype and better treatment response. Conclusion. These findings suggest that ABCB1 loci on exon 21 G2677T and exon 26 C3435T may have predictive value as pharmacogenetic markers for olanzapine/risperidone-induced metabolic disturbances, and treatment response in female schizophrenic patients.

metabolic abnormalities; second generation of antipsychotics; ABCB1 polymorphism

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