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 TNFα 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 TNFα were genotyped using TaqMan®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα 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.
CITATION STYLE
Wood, A. M., Simmonds, M. J., Bayley, D. L., Newby, P. R., Gough, S. C., & Stockley, R. A. (2008). The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency. Respiratory Research, 9. https://doi.org/10.1186/1465-9921-9-52
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