Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia

Int J Mol Sci. 2021 Jun 22;22(13):6657. doi: 10.3390/ijms22136657.

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.

Keywords: airway epithelial cells; differentiation; inflammation; remodelling; rs16969968.

MeSH terms

  • Cell Differentiation*
  • Cells, Cultured
  • Chromosomes, Human, Pair 15
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation*
  • Lung Diseases / genetics
  • Lung Diseases / metabolism
  • Multigene Family
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Polymorphism, Single Nucleotide*
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / physiology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / physiopathology
  • Tobacco Use Disorder / genetics
  • Tobacco Use Disorder / metabolism

Substances

  • CHRNA5 protein, human
  • Nerve Tissue Proteins
  • Receptors, Nicotinic