Variability in small airway epithelial gene expression among normal smokers

Area of Science:

• Pulmonary Medicine
• Genetics
• Molecular Biology

Background:

• Cigarette smoking is a primary cause of COPD, but genetic factors likely explain why only some smokers develop the disease.
• Individual responses to smoking vary, suggesting differences in protective or susceptibility gene expression.

Purpose of the Study:

• To investigate variability in gene expression in the small airway epithelium of smokers and non-smokers.
• To identify genes that show differential expression in response to smoking and vary between individuals.

Main Methods:

• Gene expression was analyzed using Affymetrix arrays and quantitative polymerase chain reaction.
• Small airway epithelium samples were obtained from normal non-smokers, normal smokers, and smokers with COPD.

Main Results:

• 152 smoking-responsive genes showed significant up- or down-regulation.
• Individual variability in gene expression was reproducible and observed in both normal smokers and COPD patients.
• Smokers with COPD exhibited greater variability in gene expression than normal smokers.
• Highly variable genes were involved in signal transduction, metabolism, and response to oxidants.

Conclusions:

• Genetic diversity in specific genes likely contributes to variable individual responses to smoking.
• These highly variable genes are potential candidates for assessing COPD susceptibility in future genetic studies.