Pharmaco-genetic analysis of CYP1A1 and RGS4 variants and its impact on response to olanzapine and risperidone in Indian schizophrenic cohort

摘要

Objectives: Genetic variations contribute significantly to inter-individual responses to drugs and side effects. Pharmacogenomics has the potential to be utilized as a tool in disorders like schizophrenia with a high degree of genetic inheritance, although data on pharmacogenomics of schizophrenia are limited. Olanzapine and risperidone are the frequently used anti-psychotic drugs used in clinics. Studies have observed the variability in the response of both drugs in schizophrenic individuals. Considering the pharmacogenomics importance of both drugs, we aim to examine the cytochrome P 4501A1 (CYP1A1) and regulator of G-protein signaling 4 (RGS4) variants and their metabolizing status in 94 schizophrenic individuals of Indian descent. Methods: The present study is retrospective observational study. The metabolizing status of schizophrenic individuals was examined using Axiom Precision Medicine Diversity Array (PMDA) and the data were analyzed with the help of SNP Axiom Analysis Suite v5.1 (Affymetrix). The pharmacogenomics annotation was performed using PharmGKB. Results: Genotype and allele frequencies were observed. The results reveal the high frequency of poor metabolizers of olanzapine and risperidone in the studied cohort. In lieu of the high distribution of poor metabolizers, we compare observed allele frequencies with global populations’ data to understand the variability of the genetic pool attained by Indian schizophrenic individuals. Conclusions: Interestingly, the Indian schizophrenic cohort forms a different cluster compared to global populations, suggesting that pharmacogenomics testing might play an important role in clinical decision making for schizophrenia drug management.