PI-045 - FREQUENCIES OF CLINICALLY ACTIONABLE POLYMORPHISMS, GENOTYPES, AND PHENOTYPES OF CYP2D6 AND CYP2C19 GENES IN THE CENTRAL INDIAN POPULATION WITH COMMON MENTAL DISORDERS

S. Chenchula¹, S. Atal², R. Jhaj², A. Rozatkar², T. Modak², J. Singh²; ¹ALL INDIA INSTITUTE OF MEDICAL SCIENCES, Bhopal, MADHYA PRADESH, INDIA, ²AIIMS BHOPAL, MADHYA PRADESH, INDIA.

Background: The distribution of clinically actionable cytochrome P450 2D6 (CYP2D6) and CYP2C19 alleles varies globally, with limited data available for Central India. This study aimed to determine the frequencies of clinically actionable CYP2D6 alleles (*2, *2A, *3, *4, *5, *6, *10, *41, and duplications) and CYP2C19 alleles (*2, *3, *17) in this population.

Methods: The present cross sectional study was conducted at in a tertiary care teaching institute , All India Institute of Medical Sciences, Bhopal, India, in the Dept. of Psychiatry and Clinical Pharmacology . We included a total of 316 individuals diagnosed with common mental disorders , and we analysed CYP2D6 and CYP2C19 genes using competitive allele-specific PCR (KASP) SNP genotyping and TaqMan CNV assays on the QuantStudio-5 RTPCR system

Results: The frequencies of clinically actionable CYP2D6 alleles *2, *3, *4, *5, *6, *10, *41, and duplications were 20.3%, 34.2%, 0%, 6.3%, 8.9%, 0%, 13.3%, 3.8%, and 16.7%, respectively. For CYP2C19, the frequencies of *2, *3, and *17 alleles were at 19%, 0.3%, and 6.6%, respectively.
The predicted CYP2D6 genotypes were *2/*10 at 19.6% , *2/*41 at 15.3%, *1/*2/*2x≥2 at 12% and *3/*6 at 0.9% followed by phenotypes at 57.6% NM, 13.2% UM, 1.8% PM, and 27.4% IM.
The distributed frequencies of CYP2C19 genotypes were at *2/*2 at 16.5% and *17/*17 at 2.5%, and *1/*2 at 35.4% and their phenotypes were 15.8% NM, 21.2% PM, 2.8% UM, 9.5% RM, and 50.6% IM.

Conclusion: A high prevalence of CYP2D6 gene duplications and ultra-rapid metabolizers, along with CYP2C19*2 alleles and poor metabolizers, was observed in the central Indian population with CMDs . These findings underscore the importance of routine CYP2D6 and CYP2C19 genotyping for patients in Central India receiving medications metabolized by these enzymes