Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease

• Published in: Genes and immunity Vol. 3; no. 7; pp. 400 - 406
• Main Authors: Vijgen, L, Van Gysel, M, Rector, A, Thoelen, I, Esters, N, Ceelen, T, Vangoidsenhoven, E, Vermeire, S, Rutgeerts, P, Van Ranst, M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2002
• Subjects: Adolescent; Adult; Aged; Alleles; Carrier Proteins - genetics; Child; Crohn's disease; Cytokines; Environmental factors; Etiology; Gene Frequency; Gene polymorphism; Genetic factors; Genetic Predisposition to Disease; Genotype & phenotype; Heterozygotes; Homozygotes; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein; Interleukin 1 receptors; Intestine; Intracellular Signaling Peptides and Proteins; Middle Aged; Minisatellite Repeats; Molecular Sequence Data; NOD2 protein; Nod2 Signaling Adaptor Protein; Polymorphism; Receptors, Interleukin-1 - antagonists & inhibitors; Sialoglycoproteins - genetics; Ulcerative colitis
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6363888

Both genetic and environmental factors have been implicated in the etiology of inflammatory bowel diseases (IBD) i.e., Crohn's disease (CD) and ulcerative colitis (UC). Polymorphisms in cytokine genes are likely to influence an individual's predisposition to IBD. In intron 2 of the interleukin-1 receptor antagonist (IL-1ra) gene, a variable number of an 86-bp tandem repeat (VNTR) polymorphism leads to the existence of five different alleles. In order to analyze the association between certain IL-1ra VNTR-alleles and IBD, we investigated the IL-1ra genotype and allele frequencies in 342 unrelated IBD patients and in 401 healthy control individuals. CD patients were also genotyped for the three main associated variants in the NOD2/CARD15 gene. In the IBD group, a significant decrease in the frequency of IL-1ra allele 1 (P=0.048) compared to controls was observed. The frequency of IL-1ra genotype 1/1 was significantly lower in the IBD population vs the control group (P=0.018). Analysis of the CD population without NOD2 homozygotes and compound heterozygotes revealed a more significant decrease in IL-1ra genotype 1/1 compared to controls (P=0.038). These results support the hypothesis that the IL-1ra VNTR-polymorphism could be among the genetic factors that are of importance in IBD susceptibility.