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. MATERIAL AND 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.
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. MATERIAL AND 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: Tristan M Sissung; Sarah M Troutman; Tessa J Campbell; Heather M Pressler; Hyeyoung Sung; Susan E Bates; William D Figg Journal: Discov Med Date: 2012-01 Impact factor: 2.970
Authors: Laura M Hodges; Svetlana M Markova; Leslie W Chinn; Jason M Gow; Deanna L Kroetz; Teri E Klein; Russ B Altman Journal: Pharmacogenet Genomics Date: 2011-03 Impact factor: 2.089
Authors: Vibeke Andersen; Jane Christensen; Anja Ernst; Bent A Jacobsen; Anne Tjønneland; Henrik B Krarup; Ulla Vogel Journal: World J Gastroenterol Date: 2011-01-14 Impact factor: 5.742
Authors: Vibeke Andersen; Anja Ernst; Jane Christensen; Mette Østergaard; Bent A Jacobsen; Anne Tjønneland; Henrik B Krarup; Ulla Vogel Journal: BMC Med Genet Date: 2010-05-28 Impact factor: 2.103
Authors: Hilbert S de Vries; Rene H M te Morsche; Martijn G H van Oijen; Iris D Nagtegaal; Wilbert H M Peters; Dirk J de Jong Journal: PLoS One Date: 2010-11-24 Impact factor: 3.240
Authors: Jón O Kristinsson; Paul van Westerveld; Rene H M te Morsche; Hennie M J Roelofs; T Wobbes; Ben J M Witteman; Adriaan C I T L Tan; Martijn G H van Oijen; Jan B M J Jansen; Wilbert H M Peters Journal: World J Gastroenterol Date: 2009-07-28 Impact factor: 5.742
Authors: Vibeke Andersen; Anja Ernst; Jurgita Sventoraityte; Limas Kupcinskas; Bent A Jacobsen; Henrik B Krarup; Ulla Vogel; Laimas Jonaitis; Goda Denapiene; Gediminas Kiudelis; Tobias Balschun; Andre Franke Journal: BMC Med Genet Date: 2011-10-13 Impact factor: 2.103