Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses.
17q12-q21
Bayesian methods
asthma
birth cohorts
childhood
innate immune response
interferons
rhinovirus
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
09
08
2023
revised:
23
02
2024
accepted:
01
03
2024
medline:
18
3
2024
pubmed:
18
3
2024
entrez:
17
3
2024
Statut:
aheadofprint
Résumé
Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheezing. There is little mechanistic data linking chromosome 17q12-q21 to wheezing illness. To investigate whether 17q12-q21 risk alleles may be associated with impaired interferon (IFN) responses to rhinovirus. In a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells (PBMCs) with rhinovirus-A1 (RV-A1) and rhinovirus-A16 (RV-A16) and measured IFN and IFN-induced chemokine CXCL10/IP10 responses in supernatants. We investigated associations between virus-induced cytokines and six SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants. Five SNPs (in high linkage disequilibrium, r Polymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism (impaired IFN-β induction) linking 17q12-q21 risk alleles with asthma/wheeze.
Sections du résumé
BACKGROUND
BACKGROUND
Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheezing. There is little mechanistic data linking chromosome 17q12-q21 to wheezing illness.
OBJECTIVE
OBJECTIVE
To investigate whether 17q12-q21 risk alleles may be associated with impaired interferon (IFN) responses to rhinovirus.
METHODS
METHODS
In a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells (PBMCs) with rhinovirus-A1 (RV-A1) and rhinovirus-A16 (RV-A16) and measured IFN and IFN-induced chemokine CXCL10/IP10 responses in supernatants. We investigated associations between virus-induced cytokines and six SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants.
RESULTS
RESULTS
Five SNPs (in high linkage disequilibrium, r
CONCLUSIONS
CONCLUSIONS
Polymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism (impaired IFN-β induction) linking 17q12-q21 risk alleles with asthma/wheeze.
Identifiants
pubmed: 38494094
pii: S0091-6749(24)00269-0
doi: 10.1016/j.jaci.2024.03.005
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.