PXR: A Xenobiotic Receptor of Diverse Function Implicated in Pharmacogenetics

Abstract

The pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of drug-metabolic enzymes and transporters involved in the responses of mammals to their chemical environment. The same enzyme and transporter systems are also involved in the homeostasis of numerous endogenous chemicals. The regulatory function of PXR is implicated in normal physiology and diseases, such as drug–drug interactions, hepatic steatosis, vitamin D homeostasis, bile acids homeostasis, steroid hormones homeostasis and inflammatory bowel diseases. As such, any genetic variations of this receptor could potentially have widespread effects on the disposition of xenobiotics and endobiotics. Knowledge concerning the genetic polymorphisms of PXR may help to understand the variations in human drug response and ensure safe drug use. The correlation of PXR genetic polymorphisms with several disease conditions also suggests that this receptor may represent a valid therapeutic for hepato-intestinal disorders such as inflammatory bowel disease and primary sclerosing cholangitis.

Keywords: :

• drug metabolism
• genetic variants
• pharmacogenetics
• pregnane X receptor
• splice variants

Financial & competing interests disclosure

The original results from WX‘s laboratory that are described in this article were generated with the support of National Institutes of Health (NIH) grants ES012479, CA107011 and ES014626. MDK is supported by a NIH physician-scientist career development grant K08-GM074238. he authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The original results from WX‘s laboratory that are described in this article were generated with the support of National Institutes of Health (NIH) grants ES012479, CA107011 and ES014626. MDK is supported by a NIH physician-scientist career development grant K08-GM074238. he authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.