Genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy population

Pak J Pharm Sci. 2016 May;29(3 Suppl):1037-41.

Abstract

Inter individual variability in polymorphic UDP-glucuronosyltransferase (UGT2B15) has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy (male=59 and female=50) population. The association between genotype (UGT2B15) and phenotype (paracetamol glucuronidation) has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value (0.792).

MeSH terms

  • Acetaminophen / metabolism*
  • Chromatography, High Pressure Liquid
  • Female
  • Gene Frequency
  • Genotype
  • Glucuronides / metabolism*
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism*
  • Healthy Volunteers
  • Humans
  • Male
  • Metabolic Detoxication, Phase II
  • Pakistan
  • Pharmacogenomic Testing
  • Phenotype
  • Polymorphism, Genetic*
  • Young Adult

Substances

  • Glucuronides
  • Acetaminophen
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 2B15, human