BibTex format
@article{Regis:2024:10.1016/j.jaci.2024.03.005,
author = {Regis, E and Fontanella, S and Curtin, JA and de, Moira AP and Edwards, MR and Murray, CS and Simpson, A and Johnston, SL and Custovic, A},
doi = {10.1016/j.jaci.2024.03.005},
journal = {Journal of Allergy and Clinical Immunology},
pages = {308--315},
title = {Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses},
url = {http://dx.doi.org/10.1016/j.jaci.2024.03.005},
volume = {154},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.ObjectiveWe investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus.MethodsIn 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.ResultsFive SNPs (in high linkage disequilibrium, r2 ≥ 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.ConclusionsPolymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism—impaired IFN-β induction&md
AU - Regis,E
AU - Fontanella,S
AU - Curtin,JA
AU - de,Moira AP
AU - Edwards,MR
AU - Murray,CS
AU - Simpson,A
AU - Johnston,SL
AU - Custovic,A
DO - 10.1016/j.jaci.2024.03.005
EP - 315
PY - 2024///
SN - 0091-6749
SP - 308
TI - Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses
T2 - Journal of Allergy and Clinical Immunology
UR - http://dx.doi.org/10.1016/j.jaci.2024.03.005
UR - https://www.sciencedirect.com/science/article/pii/S0091674924002690
VL - 154
ER -