title: Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population.
abstract: OBJECTIVE
  Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an impaired mucosal defence to normal constituents of the intestinal flora and a dysregulated inflammatory response. The purpose of the study was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in these processes were associated with CD and UC.
  
  
  METHODS
  Allele frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541 UC patients and 796 healthy controls.
  
  
  RESULTS
  Carriers of the homozygous COX-2 and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054), respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51) p=0.093), respectively, assuming complete dominance. No association was found for BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification of smoking habit at the time of diagnosis was found.
  
  
  CONCLUSIONS
  An effect of the COX-2 polymorphism on both CD and UC was shown which is compatible with the presence of a recessive allele in linkage equilibrium with the SNP marker in the COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak association with CD, and a marginally suggestive association with UC.
authors.affiliation: Medical Department, Viborg Regional Hospital, Viborg.
authors.forename: Mette
authors.initials: M
authors.lastname: Østergaard
authors.forename: Anja
authors.initials: A
authors.lastname: Ernst
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Labouriau
authors.forename: Enrika
authors.initials: E
authors.lastname: Dagiliené
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Krarup
authors.forename: Mariann
authors.initials: M
authors.lastname: Christensen
authors.forename: Niels
authors.initials: N
authors.lastname: Thorsgaard
authors.forename: Bent A
authors.initials: BA
authors.lastname: Jacobsen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tage-Jensen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003718:Denmark; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2