CEACAM3 decreases asthma exacerbations and modulates respiratory syncytial virus latent infection in children
Journal
Thorax
Journal Volume
75
Journal Issue
9
Pages
725-734
Date Issued
2020
Author(s)
Abstract
Background Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations. Objective The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations. Methods We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations. Results A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes (GADD45A, GYPB, MS4A3, NFE2, RNASE3, EPB41L3, CEACAM6 and CEACAM3) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 (CEACAM3) significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with CEACAM3 mRNA expression in lung tissue (p for trend=1.2×10 -7). CEACAM3 mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets. Conclusions rs7251960 is an eQTL for CEACAM3, and CEACAM3 mRNA expression is reduced in subjects experiencing asthma exacerbations. CEACAM3 may be a modulator of RSV latent infection on asthma exacerbations. ?
SDGs
Other Subjects
DNA; messenger RNA; actin binding protein; carcinoembryonic antigen; CEACAM3 protein, human; CEACAM6 protein, human; cell adhesion molecule; cell cycle protein; eosinophil cationic protein; EPB41L3 protein, human; GADD45A protein, human; glycosylphosphatidylinositol anchored protein; GYPB protein, human; immunoglobulin M; leukocyte antigen; membrane protein; messenger RNA; MS4A3 protein, human; NFE2 protein, human; RNASE3 protein, human; transcription factor NF E2 p45 subunit; Article; asthma; CEACAM3 gene; CEACAM6 gene; child; controlled study; disease exacerbation; EPB41L3 gene; female; GADD45A gene; gene; gene expression; gene identification; gene interaction; genetic analysis; genotype; GYPB gene; human; human tissue; lung parenchyma; major clinical study; male; MS4A3 gene; NFE2 gene; nose mucosa; priority journal; quantitative trait locus; respiratory syncytial virus infection; RNASE3 gene; single nucleotide polymorphism; validation process; adolescent; asthma; blood; complication; disease exacerbation; gene expression profiling; genetics; immunology; infection; lung; meta analysis; metabolism; pathophysiology; recurrent disease; respiratory mucosa; respiratory syncytial virus infection; virology; Adolescent; Antigens, CD; Asthma; Carcinoembryonic Antigen; Cell Adhesion Molecules; Cell Cycle Proteins; Child; Disease Progression; Eosinophil Cationic Protein; Female; Gene Expression Profiling; Genotype; Glycophorins; GPI-Linked Proteins; Humans; Immunoglobulin M; Latent Infection; Lung; Male; Membrane Proteins; Microfilament Proteins; NF-E2 Transcription Factor, p45 Subunit; Polymorphism, Single Nucleotide; Respiratory Mucosa; Respiratory Syncytial Virus Infections; RNA, Messenger; Symptom Flare Up
Publisher
BMJ Publishing Group
Type
journal article