Abstract
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.
Highlights
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
Homozygous variant allele carriers were at 2.48-fold increased risk of CD and heterozygous carriers were at 1.31-fold increased risk of CD after adjusting for age, gender and smoking status (Table 2)
Homozygous variant allele carriers were at 2.31-fold increased risk of UC and heterozygous carriers were at 1.34-fold increased risk of UC after adjusting for age, gender and smoking status (Table 3)
Summary
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. The chronic inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are complex diseases caused by an interplay between genetic and environmental factors [1]. The recent years have brought much progress regarding the genetics in IBD and the number of confirmed IBD associated loci and genes have risen dramatically [2,3,4,5,6,7]. Northern European populations, including the Danish, generally have low frequencies of the CD risk-associated variants of CARD15 [3,10], and it is of interest to search for more genetic determinants in these populations. Differences in environmental exposures and genetic heterogeneity between ethnic groups may have complicated the search for genetic and gene-environmental determinants
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