Polymorphisms in the IL 18 gene are associated with specific sensitization to common allergens and allergic rhinitis.
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 levels (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 < or =.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).


CONCLUSIONS
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.
Kruse
Susanne
S
Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
Kuehr
Joachim
J
Moseler
Michael
M
Kopp
Matthias V
MV
Kurz
Thorsten
T
Deichmann
Klaus A
KA
Foster
Paul S
PS
Mattes
Joerg
J
D000483:Alleles; D000485:Allergens / Q000276:immunology*; D005091:Exons; D006801:Humans; D007114:Immunization; D020382:Interleukin-18 / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics / Q000276:immunology*
D000485:Allergens; D020382:Interleukin-18