IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

BMC Pulm Med. 2018 Mar 21;18(1):51. doi: 10.1186/s12890-018-0616-6.

Abstract

Background: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations?

Methods: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months.

Results: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3.

Conclusion: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.

Trial registration: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.

Keywords: Biomarker; Cohort; Interleukin 28B; Mortality; Single nucleotide polymorphisms.

Publication types

  • Observational Study

MeSH terms

  • Adrenomedullin / blood
  • Aged
  • Atrial Natriuretic Factor / blood
  • Case-Control Studies
  • Cohort Studies
  • Disease Progression
  • Dyspnea
  • Female
  • Forced Expiratory Volume
  • Glycopeptides / blood
  • Humans
  • Interferons
  • Interleukins / blood
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Procalcitonin / blood
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Protein Precursors / blood
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index

Substances

  • Glycopeptides
  • IFNL3 protein, human
  • IFNL4 protein, human
  • Interleukins
  • Procalcitonin
  • Protein Precursors
  • copeptins
  • proadrenomedullin
  • Adrenomedullin
  • Atrial Natriuretic Factor
  • Interferons