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