UGT1A9 Genetic Polymorphisms and Raloxifene Pharmacogenetics
Abstract
The goal of this DOD Breast Concept award was to identify and functionally characterize common genetic polymorphisnis in the human UDP-glucuronosyltransferase gene, UGTlA9. We had previously determined that UGTlA9, a metabolic enzyme expressed predominantly in the human liver, catalyzed the glucuronidatic and inactivation of the antiestrogen raloxifene (RAL). The phannacokinetics of RAL is known to be subject to significant interindividual variation, possibly associated with variable clinical efficacy. We hypothesized that genetic variation in the human UGTlA9 gene contributed to variable pharmacokinetics of RAL and therefore sought to characterize genetic polymorphisms within this gene. We describe here the identification of five common genetic polymorphisms within the human UGTlA9 gene. None of those polymorphisms altered encoded amino acid sequence. However, one variable length nucleotide repeat (VLNR) was within the putatiy TATAA box promoter. The function of this polymorphism is currently under investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA405339
Entities
People
- Rebecca B. Raftogianis
Organizations
- Fox Chase Cancer Center