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

Wood, Alice M., Simmonds, Matthew J., Bayley, Darren L. , Newby, Paul R., 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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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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