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

Alice M Wood¹ , Matthew J Simmonds¹ , Darren L Bayley² , Paul R Newby¹ , Stephen C Gough¹ and Robert A Stockley²

¹Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK

²Lung Investigation Unit, University Hospital Birmingham, Birmingham, B15 2TH, UK

author email corresponding author email

Respiratory Research 2008, 9:52doi:10.1186/1465-9921-9-52


Published:	11 July 2008

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 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.