title: Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's Disease.
abstract: Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.
authors: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. karin.h.franzen@oru.se
authors: Karin
authors: K
authors: Fransén
authors: Petra
authors: P
authors: Franzén
authors: Anders
authors: A
authors: Magnuson
authors: Ali Ateia
authors: AA
authors: Elmabsout
authors: Nils
authors: N
authors: Nyhlin
authors: Anna
authors: A
authors: Wickbom
authors: Bengt
authors: B
authors: Curman
authors: Leif
authors: L
authors: Törkvist
authors: Mauro
authors: M
authors: D'Amato
authors: Johan
authors: J
authors: Bohr
authors: Curt
authors: C
authors: Tysk
authors: Allan
authors: A
authors: Sirsjö
authors: Jonas
authors: J
authors: Halfvarson
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; D000072516:Retinoic Acid 4-Hydroxylase
references: Gene. 2004 Mar 17;328:1-16
references: 15019979
references: J Biol Chem. 2004 Jan 2;279(1):77-85
references: 14532297
references: Gut. 2009 Jun;58(6):737-41
references: 19433589
references: Gastroenterology. 2009 Oct;137(4):1391-402.e1-6
references: 19632226
references: Am J Gastroenterol. 2010 Sep;105(9):1986-93
references: 20354506
references: Nat Rev Immunol. 2008 Sep;8(9):685-98
references: 19172691
references: Development. 1997 Jan;124(2):313-26
references: 9053308
references: J Biol Chem. 2011 Sep 23;286(38):33322-34
references: 21803772
references: Can J Gastroenterol. 2005 Sep;19 Suppl A:5A-36A
references: 16151544
references: Gut. 2003 Jan;52(1):65-70
references: 12477762
references: Gut. 2011 Dec;60(12):1739-53
references: 21300624
references: Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):875-86
references: 19519282
references: Mol Med. 2012 May 09;18:712-8
references: 22415012
references: PLoS One. 2011 Jan 07;6(1):e16089
references: 21249211
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6403-8
references: 10823918
references: Gastroenterology. 2011 May;140(5):1526-35.e3
references: 21300065
references: J Biol Chem. 1997 Jul 25;272(30):18538-41
references: 9228017
references: Nature. 1987 Dec 3-9;330(6147):444-50
references: 2825025
references: Am J Gastroenterol. 2009 Nov;104(11):2774-8
references: 19623167
references: Scand J Gastroenterol Suppl. 1989;170:2-6; discussion 16-9
references: 2617184
references: J Nutr. 2002 Sep;132(9):2743-7
references: 12221239
references: Am J Gastroenterol. 2006 Jul;101(7):1569-73
references: 16863562
references: J Immunol. 2010 May 15;184(10):5519-26
references: 20400707
references: J Neurobiol. 2006 Jun;66(7):606-30
references: 16688755
references: J Leukoc Biol. 2009 Oct;86(4):959-69
references: 19477911
references: Gut. 2012 Jun;61(6):918-32
references: 22115827
references: J Immunol. 2010 Jun 15;184(12):6799-806
references: 20488794