Polymorphisms in the IL18 gene are associated with specific sensitization to common allergens and allergic rhinitis

Abstract

Background: Atopy has been linked to chromosome 11q22, a region that harbors the IL18 gene. IL-18 enhances IL-4/IL-13 production and induces IgE production that is directly associated with the pathogenesis of atopic disorders. Objective: We sought to investigate whether genetic abnormalities in the regulatory regions of the IL18 gene predispose, in part, to susceptibility to atopy. Methods: Among a white population of 105 families, the oldest child was examined with regard to atopic phenotypes and single-nucleotide polymorphisms (SNPs) within the IL18 gene. Results: We have identified 5 novel SNPs in the IL18 gene (-920[t/c], -133[c/g], and -132[a/g] in promoter 2 [upstream of exon 2]; +179[c/a; Ser35Ser] in exon 4; and +486[c/t; Phe137Phe] in exon 6). Three SNPs are located in promoter 2, and one (-133[c/g]; nuclear factor 1 site) was significantly associated with high serum IgE leveis (P = .001; odds ratio, 3.96) and specific sensitization to common allergens (P = .005; OR, 4.12). In addition, previously identified SNPs in exon 1 (+113[t/g] and +127[c/t]) and in promoter 1 (-137[g/c], GATA3 site) of the IL18 gene were significantly associated with high IgE levels (P ≤ .005; OR, 3.27-3.90) and specific sensitization (P = .02 to .008; OR, 3.27-3.83). The SNP +127(g/t) in exon 1 was also a susceptibility locus for seasonal allergic rhinitis (P = .008; OR, 3.22). Conclusion: IL18 might be responsible for the linkage effects seen in the chromosomal region 11q22, which has been found previously with the phenotype "sensitization to mite allergen." Thus a suspected direct role of IL18 in the pathogenesis of atopy has been strengthened by the presence of 8 common SNPs in the promoter regions of IL18.