title: Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohn's disease.
abstract: 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.
authors: Research Centre, Ste-Justine Hospital, Montreal, Quebec, Canada.
authors: Alfreda
authors: A
authors: Krupoves
authors: David
authors: D
authors: Mack
authors: Ernest
authors: E
authors: Seidman
authors: Colette
authors: C
authors: Deslandres
authors: Devendra
authors: D
authors: Amre
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D019819:Budesonide / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D019819:Budesonide; D004247:DNA; D011241:Prednisone