title: Genetic analysis of MDR1 and inflammatory bowel disease reveals protective effect of heterozygous variants for ulcerative colitis.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in the multidrug transporter MDR1 have been associated with inflammatory bowel disease (IBD) in different studies. However, the data are highly controversial. Recently, 6 haplotype tagging SNPs (tSNPs), representing the haplotype variations of the MDR1 gene, were identified. The aims of this study were to genotype these variants and correlate them to disease phenotype in New Zealand IBD patients.
  
  
  METHODS
  A total of 784 IBD patients and 200 healthy subjects were genotyped for 5 tSNPs and the triallelic MDR1 variant G2677T/A using the Sequenom MassArray platform. Furthermore, the effects of these variants were examined in correlation with phenotypic clinical features.
  
  
  RESULTS
  Heterozygous carriers for the variants C1236T, rs2235046 (an SNP in intron 16), and G2677T/A showed a lower risk of developing ulcerative colitis (C1236T: odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.42-0.93, P = 0.03; G2677T/A: OR = 0.59, CI = 0.39-0.89, P = 0.02; and rs2235046: OR = 0.59, 95% CI = 0.38-0.91, P = 0.009) as compared with homozygotes. None of the analyzed markers were associated with Crohn's disease on a genotypic level. Subgroup analysis revealed an association for 2 variants with IBD when stratified for age of onset (C1236T SNP and rs3789243). The MDR1 variant C3435T was associated with disease behavior in CD (OR = 1.45, 95% CI = 1.01-2.08, P = 0.04), whereas the SNP rs3789243 was found to be associated with pancolitis in UC patients (OR = 1.35, CI = 1.00-1.82, P = 0.05).
  
  
  CONCLUSIONS
  The results of our study support the role of MDR1 as a candidate gene for ulcerative colitis. Furthermore, our results suggest the possibility of a heterozygous advantage for certain MDR1 variants for this disease.
authors.affiliation: Discipline of Nutrition, FM&HS, University of Auckland, Auckland, New Zealand. c.huebner@auckland.ac.nz
authors.forename: Claudia
authors.initials: C
authors.lastname: Huebner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Browning
authors.forename: Ivonne
authors.initials: I
authors.lastname: Petermann
authors.forename: Dug Yeo
authors.initials: DY
authors.lastname: Han
authors.forename: Martin
authors.initials: M
authors.lastname: Philpott
authors.forename: Murray
authors.initials: M
authors.lastname: Barclay
authors.forename: Richard
authors.initials: R
authors.lastname: Gearry
authors.forename: Alan
authors.initials: A
authors.lastname: McCulloch
authors.forename: Pieter
authors.initials: P
authors.lastname: Demmers
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007438:Introns; D008297:Male; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1