• Jennifer K Quint, Gavin C Donaldson, Meena Kumari, Philippa J Talmud, and John R Hurst.
• Academic Unit of Respiratory Medicine, University College London, London, UK.
• Thorax. 2011 May 1; 66 (5): 418-24.

BackgroundThe 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.ObjectiveTo assess whether the 11478G→A polymorphism is associated with attenuated α(1)-antitrypsin responses at COPD exacerbation, and therefore accelerated lung function decline.MethodsLung 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.ResultsThe 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.ConclusionThe 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.

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