We screened 290 inflammatory bowel disease patients (178 ulcerative colitis and 112 Crohn's disease) and 106 controls for IL-1beta-511 and IL-1RN*2 polymorphisms by polymerase chain reaction (PCR)-based methods.
Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05).
This article will review current progress in understanding the role of Il-1 and Il-1ra in IBD, as well as discuss recently described polymorphisms in the Il-1 gene cluster and their association with UC and CD.
The frequency of allele 2 of the IL-1ra gene in ulcerative colitis (27.0%) and Crohn's disease patients (25.5%) did not differ significantly from healthy controls (23.8%).
The IL1RN*2 phenotype is associated with ulcerative colitis and Crohn's disease, lupus erythematosus, vulvar vestibulitis, and possibly with osteoporosis and coronary artery disease.
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).
Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA-307 loci and UC, as well as polymorphisms in the NOD2 gene and CD.
The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease.
Since ulcerative colitis and Crohn's disease, which are associated with ankylosing spondylitis (AS), have been found to be variably associated with the IL-1B and the IL-1RN genes encoding interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra), we have investigated whether these polymorphisms in IL-1B and IL-1RN are also involved in AS.
Significant associations were found between Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-α G-308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was associated only with IL-1RN VNTR A2 variants.
IL-1 alpha, IL-1 beta, and IL-1ra were measured by enzyme linked immunosorbent assay (ELISA) in biopsy specimens taken from inflamed and non-inflamed colon of 60 patients with Crohn's disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls.
The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, IL1B, and IL1RN genes with risk of development of CD and with the clinicopathological profile of CD patients.
IL-1β -511 CC genotype was significantly less present in UC compared to controls, while IL-1RA Mspa-I11100 CC was significantly associated with both Crohn's disease (CD) and ulcerative colitis (UC).
No significant differences were found in the allelic frequencies or allele carriage rates of the markers in the IL-1 beta and IL-1ra genes between CD, UC, and healthy controls.
These results provide further evidence that IL-1ra is important in the predisposition to UC, there may be genetic or pathogenetic heterogeneity between different ethnic groups, and UC and CD are genetically distinct diseases.
Absence of a genetic association between IL-1RN and IL-1B gene polymorphisms in ulcerative colitis and Crohn disease in multiple populations from northeast England.
In order to study if the IL-1 beta 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-1 beta and IL-1Ra, in each of the patient groups and controls.
In addition, no significant interactions between the -94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC.