Clinical–alimentary tractThe Pregnane X Receptor Locus Is Associated With Susceptibility to Inflammatory Bowel Disease
Section snippets
Study Subjects
The study population consisted of 422 unrelated patients with IBD from clinics in St James’s Hospital, St Vincent’s Hospital, and the Adelaide and Meath Hospital in Ireland and a random sample of ethnically matched but otherwise unselected controls (n = 350). Both patients and controls were Irish white subjects. The study was approved by the institutional ethics review committees, and all patients gave informed consent. Patients were diagnosed and classified by standard endoscopic, histologic,
Quality Control
Approximately 8.5% of samples were retyped anonymously for each assay as a routine quality control to assess accuracy of genotyping. A maximum of 1 genotype differed in any of the assays, and it was a different individual in each case. The restriction fragment length polymorphism assay for the 7635 SNPs also detected only 1 data point error compared with the Amplifluor 7635 SNP assay. The overall genotype error rate was slightly less than 1%, and allele miscall frequency was 0.48%. No site
Discussion
This study showed an association between genetic variation in NR1I2 and IBD. The minor allele frequencies of −25385, −24381, and 7635 were significantly reduced in patients with IBD compared with healthy controls. These SNPs have previously been reported to have functional consequences for PXR activity. Their genotype distributions in the disease populations are compatible with a functional role in IBD. In general, there is an increasing likelihood of IBD with increasing dosage of the
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Supported by the Irish Health Research Board, the Health Education Authority Programme for Research in Third Level Institutions, and Hitachi Europe, Ltd. R.M. is a Wellcome Trust/ Health Research Board lecturer. A.-C.W. was supported by the Swedish Society of Medicine and the Swedish Research Council (grant K2003-31X-14878-01A). This project was facilitated by the European Commission-funded thematic research network, Steroids in Health and Disease (Eurosterone; QLR1-CT-1999-00762).
C.M.S.’s current affiliation is: Department of Hepatology, Beaumont Hospital, Beaumont, Dublin, Ireland.
This work was jointly supervised by D.K. and R.M.