Genetic Polymorphism of UDP-Glucuronosyltransferase

Genetic polymorphism is referred to the discontinuous interspecies genetic variability among individuals having distinct alleles on a particular locus. Genetic polymorphism of genes encoding drug-metabolizing enzymes constitutes individual’s susceptibility to drugs, affirmed by having discrete allelic frequencies by the individual, strengthening the concept of precision medicine. To combat with toxic consequences of drugs, the polymorphic genes associated with xenobiotic metabolism must be studied. Up to 70% xenobiotic elimination is believed to be dependent on UDP-glucuronosyltransferase (UGT), an enzyme encoded by polymorphic UGT1A and UGT2B genes. Both bimodal and trimodal distribution patterns of UGT have been reported in various human populations studied. Genetic polymorphisms of UGT may even lead to truncated and shorter gene with grossly diminished enzymatic activity. The extent of phenotypic alteration inflicted by genetic polymorphisms depends on its nature and position on gene locus. The different isoforms of UGT superfamily differ from each other regarding substrate specificity and selectivity. The incidence of genetic polymorphisms and associated altered gene functions results in inter-individual variability in metabolic clearance and elimination of drugs. Hence, the critical interaction between genetics and biotransformation of drugs has recently been the focus of pharmacology research.