INTERVENTION OF PHARMACOGENETIC PROFILING IN THERAPEUTICS OF KASHMIRI POPULATION, A LESSON LEARNED FROM CYP3A5*3 VARIANT

Abstract

Human Cytochrome P₄₅₀ 3A, a variant of Cytochrome P-450- dependent monooxygenases is a major drug metabolizing enzyme. CYP3A has evolved to catalyze the biotransformation of its substrate. A great deal of inter-individual variation in expression levels exists for CYP3A5 gene. The common polymorphism in CYP3A5 that induces a cryptic splice site has been shown to cause a significant reduction in its expression. Variation in CYP3A enzyme activity contributes greatly to variation in systemic clearance of CYP3A substrates and its oral bioavailability. The present study was designed to study the CYP3A5*3 polymorphism in the Kashmiri population. CYP3A5*3 genotypic status of 400 unrelated individuals of the Kashmiri population was evaluated by PCR-RFLP method. The frequency of CYP3A5 variant in Kashmiri population was found similar to Caucasian but higher than that in Chinese and Japanese population. Our finding suggest that approximately 89.5% of study population carry CYP3A5*3 genotype and thus might be at an increased risk. So, detection of CYP3A5 variant alleles and knowledge about their allelic frequency in ethnic Kashmir is might play a key player in improved therapeutic intervention in Kashmiri population.