Single Nucleotide Polymorphisms in Chemosensory Pathway Genes GNB3, TAS2R19, and TAS2R38 Are Associated with Chronic Rhinosinusitis

Int Arch Allergy Immunol. 2019;180(1):72-78. doi: 10.1159/000499875. Epub 2019 May 28.

Abstract

Background: Chronic rhinosinusitis (CRS) is a multifaceted disease with a significant genetic component. The importance of taste receptor signaling has recently been highlighted in CRS; single nucleotide polymorphisms (SNPs) of bitter tastant-responsive G-protein-coupled receptors have been linked with CRS and with altered innate immune responses to multiple bacterially derived signals.

Objective: To determine in CRS the frequency of six SNPs in genes with known bitter tastant signaling function.

Methods: Genomic DNA was isolated from 74 CRS volunteers in West Virginia, and allele frequency was determined and compared with demographically matched data from the 1,000 Genomes database.

Results: For two SNPs in a gene recently associated with bitterant signaling regulation, RGS21, there were no associations with CRS (although the frequency of the minor allele of RGS21, rs7528947, was seen to increase with increasing Lund-Mackay CT staging score). Two TAS2R bitter taste receptor gene variants (TAS2R19 rs10772420 and TAS2R38 rs713598), identified in prior CRS genetics studies, were found to have similar associations in this study.

Conclusion: Unique to our study is the establishment of an association between CRS in this patient population and GNB3 SNP rs5443, a variation in an established G protein component downstream of bitterant receptor signal transduction.

Keywords: Bitterant signaling; Chronic rhinosinusitis; Genetics; Innate immune response; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Chronic Disease
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, G-Protein-Coupled / genetics*
  • Rhinitis / diagnosis*
  • Rhinitis / genetics*
  • Rhinitis / immunology
  • Risk Factors
  • Sinusitis / diagnosis*
  • Sinusitis / genetics*
  • Sinusitis / immunology

Substances

  • GNB3 protein, human
  • Receptors, G-Protein-Coupled
  • taste receptors, type 2
  • Heterotrimeric GTP-Binding Proteins