Interleukin-18 and its three gene polymorphisms relating to allergic rhinitis

Abstract

The study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (-607 C/A, -137 G/C and -133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp. in patients with AR, and IgE levels according to particular genotypes of selected SNPs, were also determined. There were no significant differences in the distribution of single IL-18 alleles or genotypes between controls and AR patients. However, frequencies of combined IL-18 genotypes arising from combinations of the three common polymorphisms (-607, -137 and -133) were significantly different between both groups (P = 0.009, P corr < 0.05, OR = 5.35, 95% CI: 1.9-15.2). There was a marginally significant association of the IL-18-607 variant with IgE levels (P = 0.05) in patients, but not in the case of the other SNPs. Patients allergic to Alternaria, but not those allergic to other antigens, showed a significant association with the IL-18-607 polymorphism (P = 0.0037, P corr < 0.05). Results suggest that IL-18 gene variants may be one of the factors participating in the pathogenesis of AR or its intermediary phenotypes.

Haplotype analysis of the interleukin-18 gene in Czech patients with allergic disorders

“…Given the multifactorial nature of allergic diseases and the critical role of IL-18 in the allergic response, the possible association of polymorphisms in the IL-18 gene with allergic states has been investigated. Previously we demonstrated association of three polymorphisms within the IL-18 gene with atopic phenotypes like elevated IgE levels and sensitization to Alternaria alternata in patients with allergic rhinitis [18]. In this study, we screened the same three SNPs together with a newly described putative functional polymorphism Ϫ1297 C/T alone and in combination (i.e., haplotypes) in Czech patients not only with allergic rhinitis but also with other frequent and important manifestations of allergic disorders, such as asthma and eczema.…”

“…Among them, Ϫ607 A/C (rs1946518), Ϫ137 C/G (rs187238) in the promoter region, and Ϫ140 C/G (previously Ϫ133 C/G, rs4988359) in intron 1 have been studied in detail with respect to etiopathogenesis of allergic diseases [15][16][17][18] and transcriptional activity or IL-18 production by monocytes [19 -21]. Current results have indicated the inconsistent association between IL-18 gene variants and clinical/ intermediary phenotypes of allergy in different populations [15][16][17][18][22][23][24][25][26][27][28][29][30][31]. However, a novel putative functional variant Ϫ1297 C/T (rs360719) within the IL-18 promoter region that seems to have an important role in IL-18 expression was recently associated with susceptibility to SLE [32].…”

Association between polymorphisms in cytokine genes IL-17A and IL-17F and development of allergic rhinitis and comorbid asthma in Chinese subjects

“…To date, several studies have investigated single-nucleotide polymorphisms (SNPs) in genes encoding the molecules implicated in the pathogenesis of AR; including specific chemokines and their receptors [7,8], interleukins (ILs) and their receptors [9,10], eosinophil peroxidise [11] and leukotriene C4 synthase [12].…”

The Relationship between Interleukin-18 Polymorphisms and Allergic Disease: A Meta-Analysis

“…IL-18 has become recognized as an important regulator of innate and acquired immune responses and is expressed at sites of chronic inflammatory disease [10]. To date, accumulating evidence demonstrated that IL-18 synergizes with IL-12 to induce IFN- γ production and promote Th1 responses [11, 12].…”