title: Different FCER1A polymorphisms influence IgE levels in asthmatics and non-asthmatics.
abstract: BACKGROUND
  Recently, three genome-wide association studies (GWAS) demonstrated FCER1A, the gene encoding a ligand-binding subunit of the high-affinity IgE receptor, to be a major susceptibility locus for serum IgE levels. The top association signal differed between the two studies from the general population and the one based on an asthma case-control design. In this study, we investigated whether different FCER1A polymorphisms are associated with total serum IgE in the general population and asthmatics specifically.
  
  
  METHODS
  Nineteen polymorphisms were studied in FCER1A based on a detailed literature search and a tagging approach. Polymorphisms were genotyped by the Illumina HumanHap300Chip (6 polymorphisms) or MALDI-TOF MS (13 polymorphisms) in at least 1303 children (651 asthmatics) derived from the German International Study of Asthma and Allergies in Childhood II and Multicentre Asthma Genetics in Childhood Study.
  
  
  RESULTS
  Similar to two population-based GWAS, the peak association with total serum IgE was observed for SNPs rs2511211, rs2427837, and rs2251746 (mean r(2) > 0.8), with the lowest p-value of 4.37 × 10(-6). The same 3 polymorphisms showed the strongest association in non-asthmatics (lowest p = 0.0003). While these polymorphisms were also associated with total serum IgE in asthmatics (lowest p = 0.003), additional polymorphisms (rs3845625, rs7522607, and rs2427829) demonstrated associations with total serum IgE in asthmatics only (lowest p = 0.01).
  
  
  CONCLUSIONS
  These data suggest that FCER1A polymorphisms not only drive IgE levels in the general population but that specific polymorphisms may also influence IgE in association with asthma, suggesting that disease-specific mechanisms in IgE regulation exist.
authors.affiliation: Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Potaczek
authors.forename: Sven
authors.initials: S
authors.lastname: Michel
authors.forename: Vishwas
authors.initials: V
authors.lastname: Sharma
authors.forename: Sonja
authors.initials: S
authors.lastname: Zeilinger
authors.forename: Christian
authors.initials: C
authors.lastname: Vogelberg
authors.forename: Andrea
authors.initials: A
authors.lastname: von Berg
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bufe
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinzmann
authors.forename: Otto
authors.initials: O
authors.lastname: Laub
authors.forename: Ernst
authors.initials: E
authors.lastname: Rietschel
authors.forename: Burkhard
authors.initials: B
authors.lastname: Simma
authors.forename: Thomas
authors.initials: T
authors.lastname: Frischer
authors.forename: Jon
authors.initials: J
authors.lastname: Genuneit
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D017455:Receptors, IgE / Q000235:genetics* / Q000276:immunology
chemical_list: C475664:FCER1A protein, human; D017455:Receptors, IgE; D007073:Immunoglobulin E
keywords: FCER1A; IgE; high-affinity IgE receptor (α-subunit); immunoglobulin E; single-nucleotide polymorphism