{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:14:58Z","timestamp":1774124098104,"version":"3.50.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T00:00:00Z","timestamp":1215734400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and <jats:italic>TNF\u03b1<\/jats:italic> polymorphisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging <jats:italic>TNF\u03b1<\/jats:italic> were genotyped using TaqMan<jats:sup>\u00ae<\/jats:sup> genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNF\u03b1 levels were measured in all PiZZ subjects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNF\u03b1 plasma level showed no phenotypic or genotypic associations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Variation in <jats:italic>TNF\u03b1<\/jats:italic> is associated with chronic bronchitis in AATD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1465-9921-9-52","type":"journal-article","created":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T18:13:37Z","timestamp":1215800017000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency"],"prefix":"10.1186","volume":"9","author":[{"given":"Alice M","family":"Wood","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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