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        Genes Involved in Interleukin-1 Receptor Type II Activities Are Associated With Asthmatic Phenotypes

        Anne-Marie Madore,Vanessa T. Vaillancourt,Emmanuelle Bouzigon,Chloé Sarnowski,Florent Monier,Marie-Hélène Dizier,Florence Demenais,Catherine Laprise 대한천식알레르기학회 2016 Allergy, Asthma & Immunology Research Vol.8 No.5

        Purpose: Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. Methods: Two large asthma family collections, the French-Canadian Saguenay—Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. Results: One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). Conclusions: Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits.

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        TNS1 and NRXN1 Genes Interacting With Early-Life Smoking Exposure in Asthma-Plus-Eczema Susceptibility

        Margaritte-Jeannin Patricia,Vernet Raphaël,Budu-Aggrey Ashley,Ege Markus,Madore Anne-Marie,Linhard Christophe,Mohamdi Hamida,von Mutius Erika,Granell Raquell,Demenais Florence,Laprise Cathrine,Bouzigo 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.6

        Purpose: Numerous genes have been associated with allergic diseases (asthma, allergic rhinitis, and eczema), but they explain only part of their heritability. This is partly because most previous studies ignored complex mechanisms such as gene-environment (G-E) interactions and complex phenotypes such as co-morbidity. However, it was recently evidenced that the co-morbidity of asthma-plus-eczema appears as a sub-entity depending on specific genetic factors. Besides, evidence also suggest that gene-by-early life environmental tobacco smoke (ETS) exposure interactions play a role in asthma, but were never investigated for asthma-plus-eczema. To identify genetic variants interacting with ETS exposure that influence asthma-plus-eczema susceptibility. Methods: To conduct a genome-wide interaction study (GWIS) of asthma-plus-eczema according to ETS exposure, we applied a 2-stage strategy with a first selection of single nucleotide polymorphisms (SNPs) from genome-wide association meta-analysis to be tested at a second stage by interaction meta-analysis. All meta-analyses were conducted across 4 studies including a total of 5,516 European-ancestry individuals, of whom 1,164 had both asthma and eczema. Results: Two SNPs showed significant interactions with ETS exposure. They were located in 2 genes, NRXN1 (2p16) and TNS1 (2q35), never reported associated and/or interacting with ETS exposure for asthma, eczema or more generally for allergic diseases. TNS1 is a promising candidate gene because of its link to lung and skin diseases with possible interactive effect with tobacco smoke exposure. Conclusions: This first GWIS of asthma-plus-eczema with ETS exposure underlines the importance of studying sub-phenotypes such as co-morbidities as well as G-E interactions to detect new susceptibility genes.

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