CEACAM3 decreases asthma exacerbations and modulates respiratory syncytial virus latent infection in children

Thorax. 2020 Sep;75(9):725-734. doi: 10.1136/thoraxjnl-2019-214132. Epub 2020 Jun 30.


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.

Keywords: asthma genetics; asthma pharmacology; clinical epidemiology; paediatric asthma; viral infection.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Antigens, CD / genetics
  • Asthma / genetics*
  • Asthma / physiopathology
  • Asthma / virology*
  • Carcinoembryonic Antigen / genetics*
  • Cell Adhesion Molecules / genetics
  • Cell Cycle Proteins / genetics
  • Child
  • Disease Progression
  • Eosinophil Cationic Protein / genetics
  • Female
  • GPI-Linked Proteins / genetics
  • Gene Expression Profiling
  • Genotype
  • Glycophorins / genetics
  • Humans
  • Immunoglobulin M / blood
  • Latent Infection / complications
  • Latent Infection / immunology
  • Lung / metabolism
  • Male
  • Membrane Proteins / genetics
  • Microfilament Proteins / genetics
  • NF-E2 Transcription Factor, p45 Subunit / genetics
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism*
  • Respiratory Mucosa / metabolism
  • Respiratory Syncytial Virus Infections / complications*
  • Respiratory Syncytial Virus Infections / immunology
  • Symptom Flare Up


  • Antigens, CD
  • CEACAM3 protein, human
  • CEACAM6 protein, human
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • EPB41L3 protein, human
  • GADD45A protein, human
  • GPI-Linked Proteins
  • GYPB protein, human
  • Glycophorins
  • Immunoglobulin M
  • MS4A3 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • NF-E2 Transcription Factor, p45 Subunit
  • NFE2 protein, human
  • RNA, Messenger
  • Eosinophil Cationic Protein
  • RNASE3 protein, human