title: Genetic variation in genes encoding airway epithelial potassium channels is associated with chronic rhinosinusitis in a pediatric population.
abstract: BACKGROUND
  Apical 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).
  
  
  METHODS
  Single 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.
  
  
  RESULTS
  Set-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.
  
  
  CONCLUSIONS
  We have implicated two airway epithelial potassium channels as novel susceptibility loci in contributing to the pathogenesis of CRS.
authors.affiliation: Department of Otorhinolaryngology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Purkey
authors.affiliation: Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Frank
authors.initials: F
authors.lastname: Mentch
authors.affiliation: Division of Human Genetics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.affiliation: Department of Otolaryngology, Montreal General Hospital, McGill University, Montreal, Québec Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Desrosiers
authors.affiliation: Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Division of Human Genetics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Department of Otolaryngology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Elina
authors.initials: E
authors.lastname: Toskala
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000235:genetics*; D012220:Rhinitis / Q000235:genetics*; D012852:Sinusitis / Q000235:genetics*; D014132:Trachea / Q000378:metabolism*
chemical_list: D015221:Potassium Channels