Genetic Variation in Genes Encoding Airway Epithelial Potassium Channels Is Associated with Chronic Rhinosinusitis in a Pediatric Population

Michael T. Purkey,Struan F. A. Grant,Hakon Hakonarson,Jin Li,Frank Mentch,Martin Desrosiers,Elina Toskala,Yong-Gang Yao

doi:10.1371/journal.pone.0089329

Abstract

BackgroundApical potassium channels regulate ion transport in airway epithelial cells and influence air surface liquid (ASL) hydration and mucociliary clearance (MCC). We sought to identify whether genetic variation within genes encoding airway potassium channels is associated with chronic rhinosinusitis (CRS).MethodsSingle nucleotide polymorphism (SNP) genotypes for selected potassium channels were derived from data generated on the Illumnia HumanHap550 BeadChip or Illumina Human610-Quad BeadChip for 828 unrelated individuals diagnosed with CRS and 5,083 unrelated healthy controls from the Children's Hospital of Philadelphia (CHOP). Statistical analysis was performed with set-based tests using PLINK, and corrected for multiple testing.ResultsSet-based case control analysis revealed the gene KCNMA1 was associated with CRS in our Caucasian subset of the cohort (598 CRS cases and 3,489 controls; p = 0.022, based on 10,000 permutations). In addition there was borderline evidence that the gene KCNQ5 (p = 0.0704) was associated with the trait in our African American subset of the cohort (230 CRS cases and 1,594 controls). In addition to the top significant SNPs rs2917454 and rs6907229, imputation analysis uncovered additional genetic variants in KCNMA1 and in KCNQ5 that were associated with CRS.ConclusionsWe have implicated two airway epithelial potassium channels as novel susceptibility loci in contributing to the pathogenesis of CRS.

Highlights

Chronic rhinosinusits (CRS) is a spectrum of clinical disease characterized by persistent inflammation of the nasal cavity and paranasal sinuses [1]
chronic rhinosinusitis (CRS) was considered an extension of acute bacterial sinusitis and the role of bacterial infection was considered primary in the development of the disease
The aim of this study is to identify whether genetic variation within genes encoding known airway potassium channel genes is associated with chronic sinusitis in a pediatric population

Summary

Introduction

Chronic rhinosinusits (CRS) is a spectrum of clinical disease characterized by persistent inflammation of the nasal cavity and paranasal sinuses [1]. CRS was considered an extension of acute bacterial sinusitis and the role of bacterial infection was considered primary in the development of the disease. Recent research and clinical focus has shifted from a primary infectious etiology (in most cases) to chronic mucosal inflammation as the primary underlying dysfunction in CRS [2]. Observations of the sinonasal manifestations of primary ciliary dyskinesia and cystic fibrosis (CF) raise the possibility that the development of CRS may have a common genetic etiology. We sought to identify whether genetic variation within genes encoding airway potassium channels is associated with chronic rhinosinusitis (CRS)

Objectives

Methods

Results

Discussion

Conclusion