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

BMC Medical Genetics

Research Article

Henrik B Krarup¹  Anja Ernst¹  Bent A Jacobsen²  Jane Christensen³  Anne Tjønneland³  Vibeke Andersen⁴  Mette Østergaard⁵  Ulla Vogel⁶ 

[1] Department of Clinical Biochemistry, Aarhus University Hospital, DK-9100, Aalborg, Denmark;Department of Medical Gastroenterology, Aarhus University Hospital, DK-9100, Aalborg, Denmark;Institute of Cancer Epidemiology, Danish Cancer Society, DK-2100, Copenhagen, Denmark;Medical Department, Viborg Regional Hospital, DK-8800, Viborg, Denmark;Medical Department, Viborg Regional Hospital, DK-8800, Viborg, Denmark;Department of Clinical Biochemistry, Viborg Regional Hospital, DK-8800, Viborg, Denmark;National Food Institute, Technical University of Denmark, DK-2860, Søborg, Denmark;Institute for Science, Systems and Models, University of Roskilde, DK-4000, Roskilde, Denmark;National Research Centre for the Working Environment, DK-2100, Copenhagen, Denmark;

关键词: Inflammatory Bowel Disease;    Ulcerative Colitis;    Inflammatory Bowel Disease Patient;    Ulcerative Colitis Patient;    Consistent Interaction;   

DOI  :  10.1186/1471-2350-11-82

 received in 2009-10-04, accepted in 2010-05-28,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCrohns 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 (HO-1/HMOX1) is a powerful anti-inflammatory and anti-oxidant enzyme, whereas the pro-inflammatory interleukin 1β (IL-1β/IL1B) and anti-inflammatory interleukin 10 (IL-10/IL10) are key modulators for the initiation and maintenance of inflammation. We investigated whether single nucleotide polymorphisms (SNPs) in the IL-1β, IL-10, and HO-1 genes, together with smoking, were associated with risk of CD and UC.MethodsAllele frequencies of the IL-1β T-31C (rs1143627), and IL-10 rs3024505, G-1082A (rs1800896), C-819T (rs1800871), and C-592A (rs1800872) and HO-1 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.ResultsCarriers of rs3024505, a marker polymorphism flanking the IL-10 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 IL-1β, IL-10 G-1082A, C-819T, C-592A, and HO-1 gene polymorphisms and CD or UC. No consistent interactions between smoking status and CD or UC genotypes were demonstrated.ConclusionsThe rs3024505 marker polymorphism flanking the IL-10 gene was significantly associated with risk of UC and CD, whereas no association was found between IL-1β or HO-1 gene polymorphisms and risk of CD and UC in this Danish study, suggesting that IL-10, but not IL-1β or HO-1, has a role in IBD etiology in this population.

【 授权许可】

CC BY   
© Andersen et al; licensee BioMed Central Ltd. 2010