Allelic polymorphism in IL-1β and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease

Abstract

SUMMARY Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra) gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying allele 2 of this gene have increased production of IL-1Ra protein. Since the final outcome of the biological effects of IL-1β may depend on the relative proportion of these two cytokines, we have studied if a TaqI polymorphism in the IL-1β gene, which is relevant to IL-1β protein production, may be involved in the genetic susceptibility to UC and Crohn's disease (CD), in association with the established IL-1Ra gene polymorphism. Polymorphisms in the closely linked genes for IL-1β and IL-1Ra were typed in 100 unrelated Dutch patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in exon 5 of the IL-1β gene and in intron 2 of the IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based methods. The IL-1β allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1β gene polymorphism might participate synergistically with the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1β and IL-1Ra, in each of the patient groups and controls. Results indicated a significant association of this pair of genes, estimated by the odds ratio (OR) after performing Fisher's exact test, in the UC group (P= 0·023, OR = 2·81), as well as in the CD group (P= 0·01, OR = 3·79). Thus, non-carriers of IL-1β allele 2 were more often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the group of healthy controls (P= 1·00, OR = 0·92). These results suggest that the IL-1β/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel diseases.