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The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

Authors


  • SAPALDIA Team:Senior scientific team: Ph. Leuenberger (p) co-dir and U. Ackermann-Liebrich (e) co-dir J.C. Barthélémy (c), W. Berger (g), R. Bettschart (p), A. Bircher (a), K. Blaser (a), G. Bolognini (p), O. Brändli (p), M. Brutsche (p), L. Burdet (p), S. H. Downs (e/s), M. Frey (p), J. M. Gaspoz (c), M. W. Gerbase (p), D. Gold (e/c/p), W. Karrer (p), R. Keller (p), B. Knöpfli (p), N. Künzli (e/exp), A. Morabia (e), U. Neu (exp), L. Nicod (p), A. P. Perruchoud (p), M. Pons (p), N. M. Probst Hensch (e/g), Th. Rochat (p), E. Russi (p), C. Schindler (s), P. Schmid-Grendelmeyer (a), J. Schwartz (e), F. Schwarz (p), P. Straehl (exp), J. M. Tschopp (p), A. von Eckardstein (cc), J. P. Zellweger (p), E. Zemp Stutz (e). Scientific team at coordinating center: L. Bayer-Oglesby (exp), S. H. Downs (e/s), D. Felber Dietrich (c), M. Imboden (g), D. Keidel (s), P. Städele-Kessler (s), M. W. Gerbase (p) (a) allergology, (c) cardiology, (cc) clinical chemistry, (e) epidemiology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (p) pneumology, (s) statistics. Scientific team at local study sites: C. Burrus, D. Felber Dietrich, U. Egermann, M. W. Gerbase, R. Gimmi, A. Kick, N. Lutz, R Keller SAPALDIA Basel is part of the European Community Respiratory Health Survey.

Correspondence:
Nicole M. Probst-Hensch, Institute of Social & Preventive Medicine, Molecular Epidemiology/Cancer Registry, University of Zürich, Vogelsangstrasse 10, CH-8091 Zürich, Switzerland.
E-mail: Nicole.Probst@usz.ch

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.

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