Mold allergen sensitization in adult asthma according to integrin β3 polymorphisms and Toll-like receptor 2/+596 genotype.
In: ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://www.hal.inserm.fr/inserm-00744485 ; Journal of Allergy and Clinical Immunology, Elsevier, 2011, 128 (1), pp.185-191.e7. ⟨10.1016/j.jaci.2011.04.007⟩, 2011
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International audience ; 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.
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Mold allergen sensitization in adult asthma according to integrin β3 polymorphisms and Toll-like receptor 2/+596 genotype.
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| Autor/in / Beteiligte Person: | Smit, Lidwien ; Bouzigon, Emmanuelle ; Bousquet, Jean ; Le Moual, Nicole ; Nadif, Rachel ; Pin, Isabelle ; Lathrop, Mark ; Demenais, Florence ; Kauffmann, Francine ; Siroux, Valérie ; Institute for Risk Assessment Sciences Utrecht, The Netherlands (IRAS) ; Utrecht University Utrecht ; Centre de recherche en épidémiologie et santé des populations (CESP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) ; Variabilité Génétique et Maladies Humaines ; Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre d'Etude du Polymorphisme Humain (CEPH) ; Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7) ; Département pneumologie et addictologie Montpellier ; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Arnaud de Villeneuve ; Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823) ; Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre National de Génotypage (CNG) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; Supported by the French Ministry of Higher Education and Research, University Paris Diderot-Paris 7, grants from the French Agency for Environmental and Occupational Health Safety (grant AFSSET-APR-SE-2004), the French National Agency for Research (grants ANR 05-SEST-020-02/05-9-97 and ANR 06-CEBS), Merck Sharp & Dohme (MSD), Hospital program of clinical research (PHRC)-Paris, and by the Netherlands Organisation for Scientific Research (NWO) Van Gogh Programme for French-Dutch cooperation. Lidwien Smit was supported by a European Academy of Allergology and Clinical Immunology-Global Allergy and Asthma European Network (EAACI-GA2LEN) exchange fellowship award ; Epidemiological Study on the Genetics and Environment of Asthma |
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| Zeitschrift: | ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://www.hal.inserm.fr/inserm-00744485 ; Journal of Allergy and Clinical Immunology, Elsevier, 2011, 128 (1), pp.185-191.e7. ⟨10.1016/j.jaci.2011.04.007⟩, 2011 |
| Veröffentlichung: | HAL CCSD ; Elsevier, 2011 |
| Medientyp: | academicJournal |
| DOI: | 10.1016/j.jaci.2011.04.007 |
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