Validation of rapid polymerase chain reaction-based detection of all length polymorphisms in the UGT 1A1 gene promoter

Diagn Mol Pathol. 2007 Mar;16(1):50-3. doi: 10.1097/01.pdm.0000213467.91139.c9.


UDP glucuronosyltransferase (UGT) 1A1 gene promoter polymorphism can affect the expression level of the UGT 1A1 enzyme. The polymorphism consists of an insertion of a TA nucleotide sequence into a (TA)6TAA sequence in the gene promoter resulting in (TA)7TAA (UGT1A1*28). This results in a reduced UGT 1A1 expression with 70% less glucuronidation capacity for bilirubin and other UGT1A1 substrates. Other polymorphisms include (TA)8TAA (UGT1A1*37) and (TA)5TAA (UGT1A1*36). The longer the TA repeats the lower the enzyme expression level. The anticancer agent irinotecan is metabolized to the active SN-38, which is further glucuronidated and detoxified by UGT 1A1. Decreased glucuronidation leads to SN-38 accumulation with severe neutropenia and diarrhea. We have developed a rapid polymerase chain reaction (PCR)-based detection of all length polymorphisms in the UGT 1A1 gene promoter. It uses PCR and DNA fragment analysis using an ABI Genetic Analyzer. Thirty-two blood samples were analyzed for UGT 1A1 promoter polymorphism. We found 2 (TA)(5)TAA/(TA)(5)TAA, 4 (TA)(5)TAA/(TA)(6)TAA, 2 (TA)(5)TAA/(TA)(7)TAA, 9 (TA)(6)TAA/(TA)(6)TAA, 11 (TA)(6)TAA/(TA)(7)TAA, 2 (TA)(7)TAA/(TA)(7)TAA, and 2 (TA)(7)TAA/(TA)(8)TAA in our sample group. To confirm the results, 6 samples with different repeats were also analyzed by DNA sequencing method. This is a rapid and reliable method for analysis of the promoter length polymorphisms of UGT 1A1 gene.

Publication types

  • Validation Study

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • DNA / analysis
  • Glucuronosyltransferase / genetics*
  • Humans
  • Irinotecan
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Genetic*
  • Prodrugs / pharmacokinetics*
  • Promoter Regions, Genetic / genetics


  • Antineoplastic Agents, Phytogenic
  • Prodrugs
  • Irinotecan
  • DNA
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Camptothecin