Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia

Author:

Diabasana Zania,Perotin Jeanne-Marie,Belgacemi Randa,Ancel JulienORCID,Mulette Pauline,Launois Claire,Delepine Gonzague,Dubernard XavierORCID,Mérol Jean-Claude,Ruaux Christophe,Gosset PhilippeORCID,Maskos Uwe,Polette Myriam,Deslée Gaëtan,Dormoy ValérianORCID

Abstract

The gene cluster region, CHRNA3/CHRNA5/CHRNB4, encoding for nicotinic acetylcholine receptor (nAChR) subunits, contains several genetic variants linked to nicotine addiction and brain disorders. The CHRNA5 single-nucleotide polymorphism (SNP) rs16969968 is strongly associated with nicotine dependence and lung diseases. Using immunostaining studies on tissue sections and air-liquid interface airway epithelial cell cultures, in situ hybridisation, transcriptomic and cytokines detection, we analysed rs16969968 contribution to respiratory airway epithelial remodelling and modulation of inflammation. We provide cellular and molecular analyses which support the genetic association of this polymorphism with impaired ciliogenesis and the altered production of inflammatory mediators. This suggests its role in lung disease development.

Funder

Université de Reims Champagne-Ardenne

Institut National de la Santé et de la Recherche Médicale

Institut de Recherche en Santé Publique - Institut National du Cancer

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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