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Background: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16)gene maps to this region. CC16is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16gene (A38G)was previously associated with asthma. Objective: We evaluated the role of the CC16SNP in pediatric asthma and asthma severity in 2 German study populations. Methods: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the pres-ent study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. Results: No association of the CC16*38Aallele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC20FEV1values were significantly lower in individuals homozygous or heterozygous for the CC16*38Aallele compared with those in subjects with the CC16*38GGgenotype (P< .05 and P< .03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1after exercise when homozygous for the CC16*38Aallele compared with that seen in asthmatic patients with the *38AGor *38GGgenotype (P< .04 and P= .006, respectively). Conclusion: We conclude that the CC16*A38GSNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children. (J Allergy Clin Immunol 2003;111:515-9.)

Background: Atopy has been linked to chromosome 11q22, a region that harbors the IL18gene. 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 IL18gene 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 IL18gene. Results: We have identified 5 novel SNPs in the IL18gene (–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 IL18gene 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: IL18might 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 IL18in the pathogenesis of atopy has been strengthened by the presence of 8 common SNPs in the promoter regions of IL18. (J Allergy Clin Immunol 2003;111:117-22.)