SERPINA1 11478G→A variant, serum α1-antitrypsin, exacerbation frequency and FEV1 decline in COPD

Thorax. 2011 May;66(5):418-24. doi: 10.1136/thx.2010.152975. Epub 2011 Feb 18.

Abstract

Background: The α(1)-antitrypsin 11478G→A polymorphism may be associated with attenuated acute α(1)-antitrypsin responses. It was hypothesised that patients with chronic obstructive pulmonary disease (COPD) and this mutation have accelerated lung function decline.

Objective: To assess whether the 11478G→A polymorphism is associated with attenuated α(1)-antitrypsin responses at COPD exacerbation, and therefore accelerated lung function decline.

Methods: Lung function decline by genotype was examined in the English Longitudinal Study of Ageing (ELSA; n=1805) and Whitehall II (n=2733) studies. 204 patients with COPD were genotyped in the London cohort and serum α(1)-antitrypsin concentration was measured at baseline and (n=92) exacerbation.

Results: The 11478G→A genotype frequencies did not vary between COPD cases and controls, or between COPD frequent and infrequent exacerbators. Subjects with the rare A allele experienced more rapid lung function decline in the Whitehall II (A vs non-A: 16 vs 4 ml/year p=0.02) but not ELSA (29 vs 34 ml/year, p=0.46) or London cohorts (26 vs 38 ml/year, p=0.06). Decline was not greater in frequent exacerbator A versus non-A carriers (20 vs 24 ml/year, p=0.58). Upregulation of α(1)-antitrypsin at exacerbation was not demonstrated, even in patients homozygous for the common allele (median exacerbation change -0.07 g/l 11478GG, p=0.87 and -0.09 g/l 11478AA/GA, p=0.92; p=0.90 for difference). In patients with the A allele, there was no correlation between serum α(1)-antitrypsin and serum interleukin 6 (IL-6) concentrations.

Conclusion: The 11478G→A α(1)-antitrypsin polymorphism is not associated with increased risk of developing COPD, nor accelerated lung function decline. Serum α(1)-antitrypsin may not be upregulated early at COPD exacerbation. In patients with the 11478G→A polymorphism there was no relationship between the serum α(1)-antitrypsin and serum IL-6 concentrations.

Publication types

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

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Disease Progression
  • Female
  • Forced Expiratory Volume / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • alpha 1-Antitrypsin / blood*
  • alpha 1-Antitrypsin / genetics

Substances

  • Biomarkers
  • Interleukin-6
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • C-Reactive Protein