The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency

Wood, Alice M. and Simmonds, Matthew J. and Bayley, Darren L. and Newby, Paul R. and Gough, Stephen C. and Stockley, Robert A. (2008) The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency. Respiratory Research, 9 (52). ISSN 1465-9921

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Abstract

Background: 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 TNF alpha polymorphisms.Methods: 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 TNF alpha were genotyped using TaqMan®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNF alpha levels were measured in all PiZZ subjects.Results: 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. TNFα plasma level showed no phenotypic or genotypic associations.Conclusion: Variation in TNFα is associated with chronic bronchitis in AATD. © 2008 Wood et al; licensee BioMed Central Ltd.

Keywords:alpha 1 antitrypsin, SERPINA1 protein, human, tumor necrosis factor alpha, adult, alpha 1 antitrypsin deficiency, article, blood, case control study, chronic bronchitis, chronic obstructive lung disease, female, genetic predisposition, genetics, human, male, metabolism, middle aged, phenotype, single nucleotide polymorphism, Adult, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency, Bronchitis, Chronic, Case-Control Studies, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Tumor Necrosis Factor-alpha
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22618
Deposited On:01 Apr 2016 09:47

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