Interaction between filaggrin null mutations and tobacco smoking in relation to asthma

• Published in: Journal of allergy and clinical immunology 2012-02, Vol.129 (2), p.374-380.e2
• Main Authors: Berg, Nikolaj Drimer, MSc, PhD, Husemoen, Lise Lotte N., MSc, PhD, Thuesen, Betina Heinsbæk, MSc, PhD, Hersoug, Lars-Georg, MSc, PhD, Elberling, Jesper, MD, PhD, Thyssen, Jacob Pontoppidan, MD, PhD, Carlsen, Berit Christina, MD, PhD, Johansen, Jeanne Duus, DMSc, Menné, Torkil, DMSc, Bønnelykke, Klaus, MD, PhD, Stender, Steen, DMSc, Meldgaard, Michael, MSc, PhD, Szecsi, Pal Bela, DMSc, Linneberg, Allan, MD, PhD
• Format: Article
• Language: English
• Subjects: 2282del4; Adolescent; Adult; Aged; Allergies; Allergy and Immunology; Asthma; Asthma - blood; Asthma - genetics; Asthma - physiopathology; Biological and medical sciences; Dermatitis, Allergic Contact - blood; Dermatitis, Allergic Contact - genetics; Dermatitis, Allergic Contact - physiopathology; Eczema; Female; filaggrin; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gene-environment interaction; Genotype; Genotype & phenotype; health examination; Health2006; Humans; Hypersensitivity, Immediate - blood; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - physiopathology; Immunoglobulin E - blood; Immunopathology; Intermediate Filament Proteins - genetics; Keratin; Male; Medical sciences; Middle Aged; Mortality; Mutation; Nitric oxide; population based; Questionnaires; R501X; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Smoking; Smoking - genetics; Spirometry; Studies; tobacco smoking; Tobacco, tobacco smoking; Toxicology; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.08.045

Background The mechanisms underlying the association between filaggrin ( FLG ) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. Objective We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. Methods A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. Results The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV1 /forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status ( P  = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma ( P  = .03) and decreased FEV1 /forced vital capacity ratio ( P  = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG -smoking interaction mainly played a role in nonatopic subjects. Conclusion FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.