Background:: Corticosteroids (CS) effectively induce remission in patients with moderate to severe Crohn's disease (CD). However, CS dependence in children is a significant clinical problem associated with numerous side effects. Identification of molecular markers of CS dependence is of paramount importance. The ABCB1 gene codes for P‐glycoprotein, a transporter involved in the metabolism of CS. We examined whether DNA variation in the ABCB1 gene was associated with CS dependency in children with CD.
Methods:: A retrospective study was carried out in two Canadian tertiary pediatric gastroenterology centers. Clinical information was abstracted from medical charts of CD patients (N = 260) diagnosed with CD prior to age 18 and administered a first course of CS during the 1 year since diagnosis. Patients were classified as CS‐dependent if they relapsed during drug tapering or after the end of therapy. DNA was extracted from blood or saliva. Thirteen tagging single nucleotide polymorphisms (tag‐SNPs) and a synonymous variation (C3435T) in the ABCB1 gene were genotyped. Allelic, genotype, and haplotype associations were examined using logistic regression and Haploview.
Results:: Tag‐SNP rs2032583 was statistically significantly associated with CS dependency. The rare C allele of this SNP (odds ratio [OR] = 0.56, 95% confidence interval [CI]: 0.34–0.95, P = 0.029) and heterozygous genotype TC (OR = 0.52, 95% CI: 0.28–0.95, P = 0.035) conferred protection from CS dependency. A three‐marker haplotype was significantly associated with CS dependence (multiple comparison corrected P‐value = 0.004).
Conclusions:: Our results suggest that the ABCB1 gene may be associated with CS dependence in pediatric CD patients. (Inflamm Bowel Dis 2011;)
1Research Centre, Ste‐Justine Hospital, Montreal, Quebec, Canada
2Department of Preventive & Social Medicine, University of Montreal, Montreal, Quebec, Canada
3Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
4Department of Medicine, Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
5Department of Paediatrics, University of Montreal, Montreal, Quebec, Canada
*Reprints: Research Centre, Bureau A‐728, Ste‐Justine Hospital, 3175 Cote‐Sainte‐Catherine, Montreal, QC, H3T 1C5 Canada
Received 30 October 2010; Accepted 10 November 2010
Published online 6 January 2011 in Wiley Online Library (wileyonlinelibrary.com).
Dr. Krupoves is supported by a scholarship from the Sainte‐Justine Hospital Foundation and by a scholarship of the PhD Program of the University of Montreal. This research was supported by the Canadian Institutes of Health Research (MOP 86609), the Canadian Institutes of Health Research, IBD‐Net Grant, Infection and Immunity, and the Sainte‐Justine Hospital Foundation.