Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function

Area of Science:

• Genomics and Respiratory Medicine
• Molecular Biology and Genetics
• Environmental Health Sciences

Background:

• Cigarette smoking is a leading cause of preventable death and chronic diseases, including COPD.
• Smoking induces transcriptional changes in the respiratory tract, but genetic influences on these changes and their impact on lung repair are poorly understood.

Purpose of the Study:

• To investigate genetic variations (eQTLs) influencing gene expression in response to acute cigarette smoke exposure.
• To determine how these genetic changes affect lung epithelial repair mechanisms.

Main Methods:

• A candidate-based eQTL study was conducted on bronchial epithelial cells after cigarette smoke exposure.
• CRISPR-Cas9 technology was used to create lung epithelial knockout cells for studying the role of FPR1.
• Gene expression and lung function were analyzed in relation to a specific SNP (rs3212855).

Main Results:

• A significant inducible eQTL (rs3212855) was identified, associated with increased expression of FPR1, FPR2, and FPR3 genes upon smoking.
• The minor allele of rs3212855 correlated with reduced lung function.
• FPR1 knockout lung epithelial cells showed protection against cigarette smoke extract-induced impairment in repair capacity.

Conclusions:

• A novel smoking-related eQTL influences FPR gene expression and is linked to diminished lung function.
• Down-regulation of FPR1 in lung epithelial cells mitigates smoke-induced damage and enhances repair capacity.