Genomic DNA from 2823 individuals of Caucasian origin including 859 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1500 healthy, unrelated controls was analyzed for eight PXR/NR1I2 single nucleotide polymorphisms (SNPs) (rs12721602 (-25564), rs3814055 (-25385), rs1523128 (-24756), rs1523127 (-24381), rs45610735 = p.Gly36Arg (+106), rs6785049 (+7635), rs2276707 (+8055), and rs3814057 (+11156)).
Carriers of two copies of the ATG haplotypes of NR1I2-rs1523130, rs3814055 and rs1523127 were 19% less sensitive to thrombocytopenia than those harboring other haplotypes (p = 0.025).
In CD, the strongest disease association was found for a haplotype consisting of the SNPs rs12721602-rs3814055-rs1523128-rs1523127-rs12721607-rs6785049-rs2276707-rs3814057 (omnibus P-value: 6.50 × 10(-15)) which was found in two separate cohorts (cohort I = discovery cohort: CD: n = 492, controls: n = 793; P = 4.51 × 10(-17); Bonferroni corrected: P = 1.27 × 10(-15); cohort II = replication cohort: CD: n = 367, controls: n = 707; P = 7.12 × 10(-4); P(corr) = 1.99 × 10(-2)).