rs2276707

This pharmacogenetic study examined SNPs in NR1I2, CYP3A4, and CYP3A5 genes in 311 Chinese breast cancer patients undergoing AC (doxorubicin/cyclophosphamide) chemotherapy. The CYP3A5*3 variant rs776746 showed strong association with grade 4 chemotherapy-induced neutropenia in multivariate analysis (OR=2.56, P=0.023), with a 3.14-fold increased risk in A-allele carriers with normal baseline ANC (P=0.004). The study demonstrates gene-environment interaction in chemotherapy toxicity prediction.

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 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.