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.

Genetic Polymorphisms of the Interleukin-1 beta (IL-1.BETA.) -511 and +3954 Single Nucleotide Polymorphisms (SNPs) in Malaysian Systemic Lupus Erythematosus (SLE) Patients

“…25,26) Others have suggested that this SNP may interrupt the IL-1β production regulation mechanism or decrease the level of IL-1ra, which will then increase the production or in vivo activities of IL-1β. 27) Surprisingly, our findings were contradictory with a few preceeding studies investigating the association between IL-1β and the onset of SLE in different populations. In a study carried out by Parks and his collaborators based on a Caucasian population in southeast of the United States, it was revealed that the −511 C/T was significantly associated to SLE.…”

Atherosclerosis as an Inflammatory Disease

“…These same genes may now confer selective disadvantages in modern times, particularly given the average life span increases, environmental stresses, and western diet/lifestyle that could lead to insulin resistance and atherosclerosis [156][157][158].…”

Significance of IL-1RA Polymorphism in Iranian Patients with Inflammatory Bowel Disease

“…IL-1b ?5887 polymorphism alters IL-1b production following lipopolysaccharide (LPS) stimulation in vitro [36]. However, IL-1b ?5887 genotype was not significantly different between patients and controls [36][37][38][39][40]. IL-1b ?5887 did not have a significant association with anatomic location of the disease [39,40].…”