The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study.
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.
Imboden
M
M
Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine & Clinical Pathology, Zurich, Switzerland.
Nicod
L
L
Nieters
A
A
Glaus
E
E
Matyas
G
G
Bircher
A J
AJ
Ackermann-Liebrich
U
U
Berger
W
W
Probst-Hensch
N M
NM
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
D020382:Interleukin-18