Tumour necrosis factor gene polymorphisms are associated with COPD.
M R Gingo1, L J Silveira, Y E Miller
1Dept of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA.
The European Respiratory Journal
|February 8, 2008
Summary
Tumour necrosis factor (TNF) gene variations influence chronic obstructive pulmonary disease (COPD) susceptibility in smokers. Specific TNF polymorphisms, like -308A, increase COPD risk, while others, like -237A, decrease it, impacting disease severity.
Area of Science:
- Genetics
- Pulmonology
- Immunology
Background:
- Tumour necrosis factor (TNF)-alpha is implicated in animal models of chronic obstructive pulmonary disease (COPD).
- Human studies on TNF gene polymorphisms and COPD susceptibility have yielded inconsistent results.
- Investigating specific TNF single nucleotide polymorphisms (SNPs) and haplotypes is crucial for understanding COPD pathogenesis.
Purpose of the Study:
- To investigate the association between six TNF SNPs and their haplotypes with COPD in Caucasian smokers.
- To determine if TNF genotypes correlate with COPD severity and lung function parameters.
Main Methods:
- Genotyping of six TNF SNPs (-1031C/T, -863C/A, -857C/T, -237G/A, -308G/A, +487G/A) and haplotypes in 423 Caucasian smokers.
- Statistical analysis including multivariate analysis and odds ratio (OR) calculations, controlling for age, sex, and pack-years.
- Assessment of lung function (forced expiratory volume in one second/forced vital capacity) and COPD severity (GOLD stages).
Main Results:
- The TNF -308 minor allele (A) was associated with an increased odds of COPD (OR 1.9) and worse lung function.
- The TNF -237 minor allele (A) showed a decreased association with COPD (OR 0.40).
- In COPD patients, the TNF -857 minor allele (T) was linked to less severe disease stages (OR 0.46), and the -1031/-863 CC/TC haplotype had a lower OR in COPD patients (OR 0.22).
Conclusions:
- Specific tumour necrosis factor (TNF) genotypes contribute to susceptibility to chronic obstructive pulmonary disease (COPD) in cigarette smokers.
- TNF gene polymorphisms influence COPD risk and disease severity.
- Further research into TNF's role in COPD pathogenesis is warranted.
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