Article Text

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

Abstract

Background The α1-antitrypsin 11478G→A polymorphism may be associated with attenuated acute α1-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 α1-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 α1-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 α1-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 α1-antitrypsin and serum interleukin 6 (IL-6) concentrations.

Conclusion The 11478G→A α1-antitrypsin polymorphism is not associated with increased risk of developing COPD, nor accelerated lung function decline. Serum α1-antitrypsin may not be upregulated early at COPD exacerbation. In patients with the 11478G→A polymorphism there was no relationship between the serum α1-antitrypsin and serum IL-6 concentrations.

  • COPD
  • α1-antitrypsin
  • exacerbation
  • lung function
  • alpha1 antitrypsin deficiency
  • COPD mechanisms
  • COPD exacerbations
  • COPD pathology

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.