Polymorphism of the interleukin‐1 receptor antagonist gene: A factor in susceptibility to rheumatoid arthritis in a Spanish population

Abstract

Objective. To assess whether an interleukin-1 receptor antagonist gene (IL1RN) polymorphism is associated with disease susceptibility and/or severity in a Spanish population of patients with rheumatoid arthritis (RA).Methods. An 86-bp variable-number tandem repeat polymorphism within IL1RN intron 2 was analyzed by polymerase chain reaction in genomic DNA obtained from 247 unrelated patients with RA (group A) and 287 healthy control subjects. The polymorphism analysis was repeated in a second group of 194 patients with RA (group B). Clinical information from patients in group A was used to compare activity and severity data in patients stratified according to the different alleles or genotypes. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to determine the strength of the association of the different alleles or genotypes with RA activity or severity.Results. In the control group, the allelic frequencies were 76% for IL1RN*1 (4 repeats), 21% for IL1RN*2 (2 repeats), 3% for IL1RN*3 (5 repeats), and 0.3% for IL1RN*4 (3 repeats). In group A patients with RA, both the frequency (OR 1.47, 95% CI 1.1-1.96, P ‫؍‬ 0.007) and carriage rate (OR 1.6, 95% CI 1.1-2.2, P ‫؍‬ 0.01) of allele IL1RN*2 were significantly increased. The increased frequency of IL1RN*2 was confirmed in group B patients with RA (OR 1.44, 95% CI 1.1-1.97, P ‫؍‬ 0.01). In patients with RA, homozygosity for IL1RN*2 was associated with an increased number of affected articular areas during the first year of followup but not with other parameters of disease activity or severity.Conclusion. Our results suggest that IL1RN has a role in determining susceptibility to RA in the Spanish population.

research paper: IL1RN VNTR and IL2−330 polymorphic genes are independently associated with chronic immune thrombocytopenia

“…It is supposed that in the presence of the polymorphism, the milieu becomes rich in proinflammatory cytokines that promote the antigen‐presenting cell/T cell and Th cell/B cell interaction. Indeed, augmented frequency of IL1RN *2 has been observed in diseases in which inflammatory or autoimmune mechanisms are involved in the pathogenesis, such as rheumatoid arthritis (Carreira et al , 2005; Jung et al , 2010) and inflammatory bowel disease (Mittal et al , 2005; Queiroz et al , 2009) as well as noncardia gastric carcinoma (El‐Omar et al , 2000; Rocha et al , 2005).…”

Graves' ophthalmopathy and gene polymorphisms in interleukin‐1α, interleukin‐1β, interleukin‐1 receptor and interleukin‐1 receptor antagonist

“…11 Cytokines production is under genetic control, and certain single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity and can alter the susceptibility to certain diseases or their clinical outcomes. 13 The IL-1 family gene SNPs have been associated with different autoimmune diseases [14][15][16][17][18][19][20][21] including Graves' disease. [22][23][24][25] However, the existing evidence regarding GO is scant.…”

Interleukin-1β, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis

“…Our results showed that IL1-RN A1A3 genotype was linked with marked RA susceptibility. Previous studies focused on the associations between specific IL-1RN VNTR alleles such as A4 [20] and A2 [19] with RA according to some, but not all studies [21,35]. To the best of our knowledge, this was the first report to document an association between A1A3 genotype and RA susceptibility.…”

“…Compared to healthy controls, RA patients had significantly higher A1A3 and À511C/C genotypes, which suggest that IL1RN and IL1-b are susceptibility loci for RA. Previous studies documented association between RA and IL-1 RN A4 allele in Taiwanese [20], and A2 allele in Spanish [19] and Chinese [24] subjects. However, the A2 allele was significantly lower in Korean RA patients [18].…”

“…A number of studies have examined the association of these polymorphisms and RA but reported controversial results [16,[18][19][20][21][22][23][24][25][26][27][28][29][30][31], possibly because of the ethnic differences, sample sizes, and patient characteristics. Until now, only one study has investigated the association between RA and genetic polymorphisms in the TNF-a gene in the Tunisian population [32].…”