Mold allergen sensitization in adult asthma according to integrin β3 polymorphisms and Toll-like receptor 2/+596 genotype

• Published in: Journal of allergy and clinical immunology Vol. 128; no. 1; pp. 185 - 191.e7
• Main Authors: Smit, Lidwien A.M., PhD, Bouzigon, Emmanuelle, MD, PhD, Bousquet, Jean, MD, Le Moual, Nicole, PhD, Nadif, Rachel, PhD, Pin, Isabelle, MD, Lathrop, Mark, PhD, Demenais, Florence, MD, Kauffmann, Francine, MD, Siroux, Valérie, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2011; Elsevier
• Subjects: Adult; Allergens; Allergens - immunology; allergy; Allergy and Immunology; Alternaria; Aspergillus; Asthma; Asthma - genetics; Asthma - immunology; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Cladosporium; epidemiology; epistasis; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Fungi; Fungi - immunology; Genetic Predisposition to Disease; genetics; Genotype; Humans; Hypersensitivity; Hypersensitivity - genetics; Hypersensitivity - immunology; Immunopathology; innate immunity; Integrin beta3; Integrin beta3 - genetics; Integrin beta3 - immunology; Life Sciences; Male; Medical sciences; Pneumology; Polymorphism, Single Nucleotide; Santé publique et épidémiologie; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Toll-Like Receptor 2; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; RR; Untranslated region; ITGB3; Linkage disequilibrium; Aspergillus; epidemiology; UTR; genetics; innate immunity; SNP; FDR; Cladosporium; SPT; Integrin β3; EGEA; OR; epistasis; Toll-like receptor 2; Alternaria; Inhaled corticosteroid; Skin prick test; allergy; asthma; Relative risk; False discovery rate; ICS; LD; Odds ratio; Single nucleotide polymorphism; Epidemiological Study on the Genetics and Environment of Asthma; TLR2; Allergy; Genetic variability; Toll like receptor 2; Natural immunity; Epistasis; Epidemiology; Fungi; Immunology; Integrin; Bronchus disease; Adult; Genetics; Mould; Sensitization; Obstructive pulmonary disease; Fungi Imperfecti; Human; Lung disease; Immunopathology; Typing; Respiratory disease; Cell adhesion molecule; Genotype; Asthma; Allergen; Polymorphism
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.04.007

Background Integrin β3 ( ITGB3 ) and Toll-like receptor 2 ( TLR2 ) are candidate genes for asthma and sensitization to mold allergens. Integrin β3 forms a complex with TLR2, and this biological interaction is required for the response of monocytes to TLR2 agonists such as fungal glucan. Objective To study whether genetic interaction between single nucleotide polymorphisms (SNPs) in genes encoding the TLR2-ITGB3 complex enhances susceptibility to mold sensitization. Methods Association analysis was conducted in 1243 adults (524 with asthma) who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma. Allergic sensitization to mold allergens was determined by skin prick testing. Association of mold sensitization with 14 ITGB3 SNPs was tested under an additive genetic model. Interaction between ITGB3 SNPs and TLR2 /+596, which was previously shown to be associated with asthma, was studied. Results A positive skin prick test to mold was found in 115 subjects with asthma (22.0%) and in 61 subjects without asthma (8.5%). The ITGB3 rs2056131 A allele was associated with mold sensitization in subjects with asthma with an odds ratio (95% CI) of 0.60 (0.43-0.83; P  = .001). Ten other ITGB3 SNPs were significantly associated with mold sensitization in TLR2 /+596TT subjects with asthma ( P  = .03-.002), whereas much weaker associations were found in carriers of the TLR2 /+596 C allele ( P  = .60-.04). Interaction between TLR2 /+596 and these  ITGB3 SNPs was statistically significant ( P interaction = .05-.001). Conclusion TLR2/+596 genotype may influence the association between ITGB3 SNPs and mold sensitization in adults with asthma.