ALLELIC POLYMORPHISM IN IL-1-BETA AND IL-1 RECEPTOR ANTAGONIST (IL-1RA) GENES IN INFLAMMATORY BOWEL-DISEASE

Recent reports have shown that allele 2 of the IL-1 receptor antagonis t (IL-1Ra) gene is overrepresented 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 o f IL-1 beta may depend on the relative proportion of these two cytokin es, we have studied if a TaqI polymorphism in the IL-1 beta gene, whic h is relevant to IL-1 beta 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 cl osely linked genes for IL-1 beta and IL-1Ra were typed in 100 unrelate d Dutch patients with UC, 79 with CD, and 71 healthy controls. The pol ymorphic regions in exon 5 of the IL-1 beta gene and in intron 2 of th e IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based m ethods. The IL-1 beta allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1 beta gene polymorphism might participate synergistically with the IL-1 Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes en coding IL-1 beta and IL-1Ra, in each of the patient groups and control s. 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-1 beta allele 2 were mor e often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the g roup of healthy controls (P = 1.00, OR = 0.92). These results suggest that the IL-1beta>/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel d iseases.