期刊
THORAX
卷 66, 期 5, 页码 418-424出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/thx.2010.152975
关键词
-
资金
- Medical Research Council (MRC)
- Economic and Social Research Council
- British Heart Foundation [RG/02/005, PG/03/029, RG/05/014]
- Health and Safety Executive
- Department of Health
- National Heart Lung and Blood Institute [HL36310]
- US NIH National Institute on Aging [AG13196]
- US NIH Agency for Health Care Policy Research [HS06516]
- John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health
- US National Institute on Aging [R01AG24233, R01AG1764406S1]
- National Institute of Aging in the USA
- UK MRC
- MRC [G0902037] Funding Source: UKRI
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [G19/35, G0100222, G8802774, G0902037] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据