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SERPINA1 11478G -> A variant, serum alpha(1)-antitrypsin, exacerbation frequency and FEV1 decline in COPD

Quint, JK; Donaldson, GC; Kumari, M; Talmud, PJ; Hurst, JR; (2011) SERPINA1 11478G -> A variant, serum alpha(1)-antitrypsin, exacerbation frequency and FEV1 decline in COPD. THORAX , 66 (5) 418 - 424. 10.1136/thx.2010.152975.

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Abstract

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

Type: Article
Title: SERPINA1 11478G -> A variant, serum alpha(1)-antitrypsin, exacerbation frequency and FEV1 decline in COPD
DOI: 10.1136/thx.2010.152975
Keywords: OBSTRUCTIVE PULMONARY-DISEASE, ALPHA-1-ANTITRYPSIN GENE, FLANKING SEQUENCE, BRONCHIAL INFLAMMATION, DNA POLYMORPHISMS, AIRWAYS DISEASE, LUNG HEALTH, DEFICIENCY, MUTATION, SPUTUM
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: http://discovery.ucl.ac.uk/id/eprint/1298732
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