title: Influence of a critical single nucleotide polymorphism on nuclear receptor PXR-promoter function.
abstract: The Pregnane and Xenobiotic Receptor (PXR; NR1I2) is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. It is expressed at higher levels primarily in liver and intestine as compared to the levels in several other organs. It is activated by a broad spectrum of xenobiotics and endobiotics. The primary function of PXR is to regulate the expression of drug metabolizing enzymes and transporters and prevent the accumulation of toxic chemicals in the body, thereby maintaining body's homeostasis. In this study, we identified a C/T single nucleotide polymorphism at position -831 from the transcriptional start site of the PXR gene promoter and examined the functional significance of this variant using both the luciferase reporter gene assays and electrophoretic mobility shift assays (EMSA). Transient transfection experiments showed that the T-allele was associated with significantly greater transcriptional activity than the C-allele of SNP rs3814055. These results indicate that the -831C/T polymorphism has a direct effect on transcriptional regulation of PXR gene. This allelic variation may be a potential genetic marker that can help identify individuals at higher risk for Inflammatory Bowel Disease (IBD).
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Manjul
authors.initials: M
authors.lastname: Rana
authors.affiliation: Department of Transfusion Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Coshic
authors.affiliation: Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Goswami
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tyagi
mesh_terms: D000483:Alleles; D002457:Cell Extracts; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011987:Receptors, Steroid / Q000235:genetics*
chemical_list: D002457:Cell Extracts; C000625852:NR1I2 protein, human; D009687:Nuclear Proteins; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid
keywords: IBD; PXR; gene expression; promoter; single nucleotide polymorphism