دورية أكاديمية
أعرض في EDS

Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses.

التفاصيل البيبلوغرافية
العنوان: Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses.
المؤلفون: Regis E; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Fontanella S; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Curtin JA; Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom., Pinot de Moira A; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Edwards MR; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Murray CS; Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom., Simpson A; Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom., Johnston SL; National Heart and Lung Institute, Imperial College London, London, United Kingdom., Custovic A; National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address: a.custovic@imperial.ac.uk.
المصدر: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Aug; Vol. 154 (2), pp. 308-315. Date of Electronic Publication: 2024 Mar 15.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: St Louis, Mosby.
مواضيع طبية MeSH: Chromosomes, Human, Pair 17*/genetics , Polymorphism, Single Nucleotide* , Rhinovirus*, Humans ; Male ; Female ; Asthma/genetics ; Asthma/immunology ; Interferons ; Child ; Respiratory Sounds/genetics ; Respiratory Sounds/immunology ; Picornaviridae Infections/immunology ; Picornaviridae Infections/genetics ; Genetic Predisposition to Disease ; Chemokine CXCL10/genetics ; Leukocytes, Mononuclear/immunology ; Child, Preschool
مستخلص: Background: Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheeze. There are few mechanistic data linking chromosome 17q12-q21 to wheezing illness.
Objective: We investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus.
Methods: In a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells with rhinovirus A1 (RV-A1) and rhinovirus A16 (RV-A16) and measured IFN and IFN-induced C-X-C motif chemokine ligand 10 (aka IP10) responses in supernatants. We investigated associations between virus-induced cytokines and 6 SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants.
Results: Five SNPs (in high linkage disequilibrium, r 2  ≥ 0.8) were significantly associated with RV-A1-induced IFN-β (rs9303277, P = .010; rs11557467, P = .012; rs2290400, P = .006; rs7216389, P = .008; rs8079416, P = .005). A reduction in RV-A1-induced IFN-β was observed among individuals with asthma risk alleles. There were no significant associations for RV-A1-induced IFN-α or CXCL10, or for any RV-A16-induced IFN/CXCL10. Bayesian profile regression analysis identified 3 clusters that differed in IFN-β induction to RV-A1 (low, medium, high). The typical genetic profile of the cluster associated with low RV-A1-induced IFN-β responses was characterized by a very high probability of being homozygous for the asthma risk allele for all SNPs. Children with persistent wheeze were almost 3 times more likely to be in clusters with reduced/average RV-A1-induced IFN-β responses than in the high immune response cluster.
Conclusions: Polymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism-impaired IFN-β induction-links 17q12-q21 risk alleles with asthma/wheeze.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: 17q12-q21; Bayesian methods; asthma; birth cohorts; childhood; innate immune response; interferons; rhinovirus
المشرفين على المادة: 9008-11-1 (Interferons)
0 (Chemokine CXCL10)
تواريخ الأحداث: Date Created: 20240317 Date Completed: 20240807 Latest Revision: 20240807
رمز التحديث: 20240808
DOI: 10.1016/j.jaci.2024.03.005
PMID: 38494094
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-6825
DOI:10.1016/j.jaci.2024.03.005