The Nicotinic Receptor Polymorphism rs16969968 Is Associated with Airway Remodeling and Inflammatory Dysregulation in COPD Patients

Genome-wide association studies unveiled the associations between the single nucleotide polymorphism rs16969968 of CHRNA5, encoding the nicotinic acetylcholine receptor alpha5 subunit (alpha 5SNP), and nicotine addiction, cancer, and COPD independently. Here, we investigated alpha 5SNP-induced epithelial remodeling and inflammatory response in human COPD airways. We included 26 alpha 5SNP COPD patients and 18 wild-type alpha 5 COPD patients in a multi-modal study. A comparative histologic analysis was performed on formalin-fixed paraffin-embedded lung tissues. Isolated airway epithelial cells from bronchial brushings were cultivated in the air-liquid interface. Broncho-alveolar fluids were collected to detect inflammatory mediators. Ciliogenesis was altered in alpha 5SNP COPD bronchial and bronchiolar epithelia. Goblet cell hyperplasia was exacerbated in alpha 5SNP small airways. The broncho-alveolar fluids of alpha 5SNP COPD patients exhibited an increase in inflammatory mediators. The involvement of the rs16969968 polymorphism in airway epithelial remodeling and related inflammatory response in COPD prompts the development of innovative personalized diagnostic and therapeutic strategies.

Automated summary

This study revealed the association between the rs16969968 polymorphism of the CHRNA5 gene and airway epithelial remodeling and inflammatory response in COPD patients. This has important implications for the development of innovative personalized diagnostic and therapeutic strategies.