Impact of rs16969968 polymorphism (SNPα5) on epithelial differentiation in COPD patients

Abstract

<b>Background:</b> Genome-wide association studies unveiled the association of <i>rs 16969968</i> present on the a5 subunit of nicotinic receptor with nicotine addiction, cancer, and chronic obstructive pulmonary disease independantly, but no biological data is available in humans. <b>Aims&amp;objectives:</b> We previously demonstrated that <i>rs 16969968</i> impaired ciliogenesis and cytokine production in respiratory epithelia. Here, we investigated the role of <i>rs 16969968</i> in the context of COPD. We suggest it is involved in bronchial and bronchiolar remodeling and differentiation and therefore participates in COPD pathogenesis. <b>Methods:</b> Lung tissues from COPD patients (n=23) were genotyped to identify the <i>rs 16969968</i> polymorphism. Immunostainings on bronchial and bronchiolar sections were performed to analyse histological features. Air-liquid interface cultures from bronchial brushings of COPD patients (n=8) were analyzed after 15 days of differentiation to assess ciliogenesis. <b>Results:</b> Bronchiolar SNPa5 COPD sections presented a 23% increase of basal cells (p&lt;0.05), and a 122% increase of Muc5ac secretory cells (p&lt;0.001), without affecting cilia. The bronchial SNPa5 COPD tissues did not differ compared to wilde-type a5. However, in vitro analysis, revealed a 33% increase of primary cilia (p&lt;0.01) in differentiated epithelia of SNPa5 COPD patients. <b>Conclusions:</b> These results highlighted the participation of SNPa5 in the remodeling of bronchial and bronchiolar epithelium, affecting the basal cells, primary cilia, and the secretion on Muc5ac in COPD patients.