The polymorphism rs3024505 proximal to IL-10 is associated with risk of ulcerative colitis and Crohns disease in a Danish case-control study

<p>Abstract</p> <p>Background</p> <p>Crohns disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (<it>HO-1/HMOX1</...

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Main Authors: Tjønneland Anne (Author), Jacobsen Bent A (Author), Østergaard Mette (Author), Christensen Jane (Author), Ernst Anja (Author), Andersen Vibeke (Author), Krarup Henrik B (Author), Vogel Ulla (Author)
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Published: BMC, 2010-05-01T00:00:00Z.
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Summary:<p>Abstract</p> <p>Background</p> <p>Crohns disease (CD) and ulcerative colitis (UC) are characterized by a dysregulated inflammatory response to normal constituents of the intestinal flora in the genetically predisposed host. Heme oxygenase-1 (<it>HO-1/HMOX1</it>) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1β (<it>IL-1β/IL1B</it>) and anti-inflammatory interleukin 10 (<it>IL-10/IL10</it>) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the <it>IL-1β</it>, <it>IL-10</it>, and <it>HO-1 </it>genes, together with smoking, were associated with risk of CD and UC.</p> <p>Methods</p> <p>Allele frequencies of the <it>IL-1β </it>T-31C (rs1143627), and <it>IL-10 </it>rs3024505, G-1082A (rs1800896), C-819T (rs1800871), and C-592A (rs1800872) and <it>HO-1 </it>A-413T (rs2071746) SNPs were assessed using a case-control design in a Danish cohort of 336 CD and 498 UC patients and 779 healthy controls. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by logistic regression models.</p> <p>Results</p> <p>Carriers of rs3024505, a marker polymorphism flanking the <it>IL-10 </it>gene, were at increased risk of CD (OR = 1.40, 95% CI: 1.06-1.85, P = 0.02) and UC (OR = 1.43, 95% CI: 1.12-1.82, P = 0.004) and, furthermore, with risk of a diagnosis of CD and UC at young age (OR = 1.47, 95% CI: 1.10-1.96) and OR = 1.35, 95% CI: 1.04-1.76), respectively). No association was found between the <it>IL-1β, IL-10 </it>G-1082A, C-819T, C-592A, and <it>HO-1 </it>gene polymorphisms and CD or UC. No consistent interactions between smoking status and CD or UC genotypes were demonstrated.</p> <p>Conclusions</p> <p>The rs3024505 marker polymorphism flanking the <it>IL-10 </it>gene was significantly associated with risk of UC and CD, whereas no association was found between <it>IL-1β </it>or <it>HO-1 </it>gene polymorphisms and risk of CD and UC in this Danish study, suggesting that <it>IL-10</it>, but not <it>IL-1β </it>or <it>HO-1, </it>has a role in IBD etiology in this population.</p>
Item Description:10.1186/1471-2350-11-82
1471-2350