PHARMACOGENOMIC ANALYSIS OF CYP2C19 VARIANTS AND THEIR PREDICTED METABOLIZER PHENOTYPES ACROSS SOUTH ASIAN, EUROPEAN AND EAST ASIAN POPULATIONS – AN IN-SILICO DESCRIPTIVE STUDY

Objectives: CYP2C19 is an important enzyme involved in the metabolism of drugs such as proton pump inhibitors, antiplatelets, and antiepileptics. Genetic variations in CYP2C19 can alter drug response and safety. This study aimed to analyze the distribution of three key CYP2C19 variants (*2, *3, *17) and predict metabolizer phenotypes across South Asian, European, and East Asian populations using in-silico methods. Methodology: Allele frequencies were obtained from gnomAD and the 1000 Genomes Project. Genotype frequencies were estimated using Hardy–Weinberg equilibrium, and metabolizer phenotypes poor, intermediate, normal, rapid, and ultrarapid were assigned. Data processing and visualization were performed using R (version 4.5.1). Results: The *2 loss-of-function allele was most frequent in South Asians (31.8%), followed by East Asians (28.0%) and Europeans (15.0%), leading to a higher proportion of poor metabolizers in South Asians. The *3 allele was rare but slightly higher in South Asians (5.7%). The *17 gain-of-function allele was most common in Europeans (22.0%), moderate in South Asians (14.0%), and rare in East Asians (2.0%). Normal metabolizers predominated in Europeans and East Asians, whereas South Asians had more intermediate and poor metabolizers. Conclusion: CYP2C19 variants show significant interethnic differences. South Asians carry more loss-of-function alleles, while Europeans have more gain-of-function variants. Population-specific pharmacogenomic insights can guide personalized drug therapy and minimize adverse effects.