Pharmacogenomic Analysis of Genetic Variability in Drug Metabolizing Enzymes-Implications for Personalized Medicine

Background: IIV is due in part to genetic polymorphisms of drug-metabolizing enzymes. This study aimed to compare variations in CYP2D6, CYP2C9, CYP3A4, and UGT1A1 enzymes and their activities in patients. Methods: Genotyping for CYP2D6 (*1A/*2G/*3T), CYP2C9 (*1C/*2T/*3A), CYP3A4 (*1A/*2G), and UGT1A1 (*28T/*36A) polymorphisms in 500 participants. Genotype frequencies were obtained and checked for compatibility with Hardy-Weinberg equilibrium. Regression analysis evaluated the relationship between genotypes and enzyme activity for each enzyme. Results: Allele frequencies which varied from 20-60% indicated that there was heterogeneity within the population. Analysis of genotype distribution revealed no deviation from Hardy-Weinberg equilibrium for any of the genotyped loci. The *1/wild-type alleles of CYP2D6, CYP2C9, and CYP3A4 had higher regression coefficients (0.45-0.55) of enzyme activity indicating that compared to variant alleles, the alleles were highly active. Comparing the two alleles for UGT1A1, *36A had a 60% higher activity versus *28T. Conclusions: As observed, polymorphisms were statistically related to variations in enzyme activity among individuals for the analyzed drug-metabolizing enzymes