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Keywords:

  • asthma;
  • atopy;
  • cohort analysis;
  • general population;
  • IL-18;
  • single-nucleotide polymorphism

Summary

Background IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma.

Objective To examine the relationship of a genetic, haplotype-tagging promotor variant −137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults.

Methods Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy.

Results The G-allele of the IL-18 promotor variant (−137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 −137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64–8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66–1.94). The interaction between IL-18 −137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype.

Conclusion Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.