rs3814057
This is a downstream gene variant variant in the NR1I2 gene.
▶Research that mentions this SNP (3)
▶Pregnane X receptor (PXR/NR1I2) gene haplotypes modulate susceptibility to inflammatory bowel diseaseAssociationN=2,823Jürgen Glas et al.(2011)· Inflammatory Bowel Diseases
A large case-control association study of 2,823 Caucasian individuals examined eight PXR/NR1I2 gene variants in 859 Crohn's disease (CD) and 464 ulcerative colitis (UC) patients versus 1,500 controls. Single SNP rs2276707 showed weak association with UC (P=0.01; OR 1.27 [1.06-1.52]), but multiple rare PXR haplotypes demonstrated strong associations with CD susceptibility (strongest omnibus P=6.50×10⁻¹⁵), suggesting PXR variants contribute to disease risk in specific IBD subgroups.
▶A Role for the Pregnane X Receptor in Flucloxacillin-Induced Liver InjuryAssociationN=205Elise Andrews et al.(2010)· Hepatology
This case-control study identifies the PXR C-25385T polymorphism (rs3814055) as a genetic risk factor for flucloxacillin-induced liver injury (DILI). The CC genotype was significantly more frequent in DILI cases (57%) versus controls (28%), with an odds ratio of 3.37 (95% CI 1.55-7.30, P=0.0023). Reporter gene assays confirmed that flucloxacillin acts as a PXR agonist, inducing PXR-regulated genes including CYP3A4 and ABCB1 in hepatocytes. The C allele shows reduced promoter activity (~4-fold lower) compared to the T allele.
▶Investigation of associations between the pregnane-X receptor gene (NR1I2) and Crohnʼs disease in Canadian children using a gene-wide haplotype-based approachAssociationN=1,001Devendra K. Amre et al.(2008)· Inflammatory Bowel Diseases
A case-control and family-based study of 270 Canadian children with Crohn's disease, 336 controls, and 395 parents found no significant associations between the NR1I2 gene (pregnane-X receptor) and pediatric CD susceptibility using eight tag-SNPs (rs1523127, rs16830505, rs2461823, rs2461818, rs6785049, rs3732359, rs1054190, rs3814057). Only rs2461823 showed marginal association (P=0.05), but this did not survive multiple testing correction. No haplotype associations were detected (omnibus P=0.61).
About NR1I2
This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]
View all NR1I2 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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