دورية أكاديمية
DNA methylation within melatonin receptor 1A (MTNR1A) mediates paternally transmitted genetic variant effect on asthma plus rhinitis
| العنوان: | DNA methylation within melatonin receptor 1A (MTNR1A) mediates paternally transmitted genetic variant effect on asthma plus rhinitis |
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| المؤلفون: | Sarnowski, Chloé, Laprise, Catherine, Malerba, Giovanni, Moffatt, Miriam, F., Dizier, Marie-Hélène, Morin, Andréanne, Vincent, Quentin, Rohde, Klaus, Esparza-Gordillo, Jorge, Margaritte-Jeannin, Patricia, Liang, Liming, Lee, Young-Ae, Bousquet, Jean, Siroux, Valérie, Pignatti, Pier Franco, Cookson, William, O. C. M., Lathrop, Mark, Pastinen, Tomi, Demenais, Florence, Bouzigon, Emmanuelle |
| المساهمون: | Variabilité Génétique et Maladies Humaines (U946), 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), Université Paris Diderot - Paris 7 (UPD7), Université du Québec à Chicoutimi (UQAC), Università degli studi di Verona = University of Verona (UNIVR), Imperial College London, McGill University and Genome Quebec Innovation Centre, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Max Delbrück Center for Molecular Medicine Berlin (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital Berlin, Harvard School of Public Health, Département pneumologie et addictologie Montpellier, Hôpital Arnaud de Villeneuve CHRU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 ) |
| المصدر: | ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://hal.science/hal-01872256Test ; Journal of Allergy and Clinical Immunology, 2016, 138 (3), pp.748 - 753. ⟨10.1016/j.jaci.2015.12.1341⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | positional cloning, DNA methylation, parent-of-origin effect, asthma, genetic association study, Linkage analysis, allergic rhinitis, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology |
| الوصف: | International audience ; BACKGROUND:Asthma and allergic rhinitis (AR) are common allergic comorbidities with a strong genetic component in which epigenetic mechanisms might be involved.OBJECTIVE:We aimed to identify novel risk loci for asthma and AR while accounting for parent-of-origin effect.METHODS:We performed a series of genetic analyses, taking into account the parent-of-origin effect in families ascertained through asthma: (1) genome-wide linkage scan of asthma and AR in 615 European families, (2) association analysis with 1233 single nucleotide polymorphisms (SNPs) covering the significant linkage region in 162 French Epidemiological Study on the Genetics and Environment of Asthma families with replication in 154 Canadian Saguenay-Lac-Saint-Jean asthma study families, and (3) association analysis of disease and significant SNPs with DNA methylation (DNAm) at CpG sites in 40 Saguenay-Lac-Saint-Jean asthma study families.RESULTS:We detected a significant paternal linkage of the 4q35 region to asthma and allergic rhinitis comorbidity (AAR; P = 7.2 × 10(-5)). Association analysis in this region showed strong evidence for the effect of the paternally inherited G allele of rs10009104 on AAR (P = 1.1 × 10(-5), reaching the multiple-testing corrected threshold). This paternally inherited allele was also significantly associated with DNAm levels at the cg02303933 site (P = 1.7 × 10(-4)). Differential DNAm at this site was found to mediate the identified SNP-AAR association.CONCLUSION:By integrating genetic and epigenetic data, we identified that a differentially methylated CpG site within the melatonin receptor 1A (MTNR1A) gene mediates the effect of a paternally transmitted genetic variant on the comorbidity of asthma and AR. This study provides a novel insight into the role of epigenetic mechanisms in patients with allergic respiratory diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27038909; hal-01872256; https://hal.science/hal-01872256Test; PUBMED: 27038909 |
| DOI: | 10.1016/j.jaci.2015.12.1341 |
| الإتاحة: | https://doi.org/10.1016/j.jaci.2015.12.1341Test https://hal.science/hal-01872256Test |
| رقم الانضمام: | edsbas.F93CEB00 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jaci.2015.12.1341 |
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