rs3814055

Case-control study of 746 Han Chinese tuberculosis patients (118 with anti-tuberculosis drug-induced liver injury [ATDILI], 628 without) genotyped for 9 SNPs in PXR and NFKB1. The T allele of rs3814055 in PXR was associated with decreased ATDILI risk (OR 0.61; 95% CI 0.42-0.89, p=0.0098), while T alleles of rs78872571 and rs4647992 in NFKB1 were associated with increased ATDILI risk (OR 1.91, p=0.028 and OR 1.81, p=0.029, respectively). This was the first study to report associations between these genetic variants and ATDILI susceptibility in a Han Chinese population.

This pharmacogenetic study of 374 patients with metastatic renal cell carcinoma examined SNP associations with sunitinib-induced toxicity. The IL8 rs1126647 T allele was associated with increased hypertension risk (OR=1.69, P=0.024), and the IL13 rs1800925 T allele was associated with increased leukopenia (OR=6.76, P=0.020) and grade >2 toxicity (OR=1.75, P=0.028). No significant associations were found with progression-free survival, overall survival, or clinical response.

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.

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.

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).

A case-control study of 365 UC and 331 CD patients versus 550 controls in a Spanish population found that the PXR gene locus (specifically a risk haplotype rs3814055*T//rs6784598*C//rs2276707*C) was significantly associated with extensive ulcerative colitis (OR=1.66, 95% CI 1.20-2.30, P=0.001). The study also identified an epistatic interaction between PXR -25385C/T and MDR1 rs3789243, where carriers of risk alleles at both loci showed increased susceptibility to extensive UC.