title: The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study.
abstract: 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.
  
  
  CONCLUSIONS
  Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.
authors.affiliation: Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine & Clinical Pathology, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Imboden
authors.forename: L
authors.initials: L
authors.lastname: Nicod
authors.forename: A
authors.initials: A
authors.lastname: Nieters
authors.forename: E
authors.initials: E
authors.lastname: Glaus
authors.forename: G
authors.initials: G
authors.lastname: Matyas
authors.forename: A J
authors.initials: AJ
authors.lastname: Bircher
authors.forename: U
authors.initials: U
authors.lastname: Ackermann-Liebrich
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: N M
authors.initials: NM
authors.lastname: Probst-Hensch
mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012882:Skin Tests; D013557:Switzerland
chemical_list: D020382:Interleukin-18