Identification of NR1I2 genetic variation using resequencing.

Authors:
Cristi R King
Cristi R King
Washington University School of Medicine
United States
Ming Xiao
Ming Xiao
Nanjing Medical University
China
Jinsheng Yu
Jinsheng Yu
Washington University School of Medicine
Matthew R Minton
Matthew R Minton
Genome Technology Access Center
Pui-Yan Kwok
Pui-Yan Kwok
University of California
United States
Howard L McLeod
Howard L McLeod
University of North Carolina
United States

Eur J Clin Pharmacol 2007 Jun 3;63(6):547-54. Epub 2007 Apr 3.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Objective: The nuclear receptor NR1I2 (also called PXR or SXR) is primarily expressed in mouse and human liver and intestines. Direct activation of NR1I2 occurs in response to a range of xenobiotics, which causes the formation of a heterodimer with the RXR receptor. This heterodimer binds to the nuclear receptor response elements of downstream genes such as ABCB1, CYP2C, and CYP3A. This study determined the extent of NR1I2 variation in three world populations.

Methods: Variation in NR1I2 was identified by pooled resequencing in African, Asian, and European populations. Validation was performed in European and African populations using PCR and Pyrosequencing technology. RNA expression of NR1I2, ABCB1 and CYP3A4 was assessed using real-time PCR.

Results: Of 36 single nucleotide polymorphisms (SNPs) identified, 24 were in the untranslated region, 8 were intronic, and 4 exonic. Thirty-six percent were unique to the African population. In comparison with previously published data, we identified 13 novel polymorphisms. The NR1I2 -566A > C polymorphism was significantly associated with ABCB1 and CYP3A4 RNA expression in colon tumor (P = 0.04 in both cases), however, this polymorphism was not associated with NR1I2 expression.

Conclusion: With NR1I2 playing such a large role in the regulation of genes involved in drug metabolism and transport, genetic variation contributing to altered NR1I2 function may have an important clinical impact.

Download full-text PDF

Source
http://link.springer.com/content/pdf/10.1007/s00228-007-0295
Web Search
http://link.springer.com/10.1007/s00228-007-0295-3
Publisher Site
http://dx.doi.org/10.1007/s00228-007-0295-3DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
June 2007
8 Reads

Publication Analysis

Top Keywords

nr1i2
9
nuclear receptor
8
polymorphism associated
8
genetic variation
8
abcb1 cyp3a4
8
rna expression
8
single nucleotide
4
pcrresults single
4
cyp3a4 assessed
4
real-time pcrresults
4
assessed real-time
4
polymorphisms snps
4
intronic exonic
4
exonic thirty-six
4
thirty-six percent
4
percent unique
4
region intronic
4
untranslated region
4
nr1i2 abcb1
4
snps identified
4

Similar Publications