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Pregnane X receptor polymorphism affects CYP3A4 induction via a ligand-dependent interaction with steroid receptor coactivator-1.

Authors
  • Lim, Yun-Ping1
  • Huang, Jin-Ding
  • 1 Institute of Basic Medical Sciences, Department of Pharmacology, Medical College, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.
Type
Published Article
Journal
Pharmacogenetics and Genomics
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Publication Date
May 2007
Volume
17
Issue
5
Pages
369–382
Identifiers
PMID: 17429319
Source
Medline
License
Unknown

Abstract

Our data indicate that the impaired induction by the Q158K variant is probably due to defective steroid receptor coactivator-1 interaction in the presence of a pregnane X receptor ligand. As the whole ligand binding domain of pregnane X receptor is required for the interaction with steroid receptor coactivator-1, we propose that, not only the Q158K variant found in Chinese, but also in native pregnane X receptor variants in other ethnic groups (D163G, A370T, R381W, and I403V) affect CYP3A4 induction by altering steroid receptor coactivator-1 recruitment.

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