title: Association study of mast cell chymase polymorphisms with atopy.
abstract: BACKGROUND
  Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene (CMA1) and atopy-related phenotypes have yielded inconsistent results.
  
  
  METHODS
  We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels <50% percentile and 24 individuals with atopic eczema and serum IgE levels >90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults (n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry).
  
  
  RESULTS
  Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline-significant association with atopic eczema, which did not remain significant after correction for multiple testing.
  
  
  CONCLUSIONS
  Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technical University Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Weidinger
authors.forename: L
authors.initials: L
authors.lastname: Rümmler
authors.forename: N
authors.initials: N
authors.lastname: Klopp
authors.forename: S
authors.initials: S
authors.lastname: Wagenpfeil
authors.forename: H J
authors.initials: HJ
authors.lastname: Baurecht
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: R
authors.initials: R
authors.lastname: Holle
authors.forename: A
authors.initials: A
authors.lastname: Gauger
authors.forename: T
authors.initials: T
authors.lastname: Schäfer
authors.forename: T
authors.initials: T
authors.lastname: Jakob
authors.forename: M
authors.initials: M
authors.lastname: Ollert
authors.forename: H
authors.initials: H
authors.lastname: Behrendt
authors.forename: H E
authors.initials: HE
authors.lastname: Wichmann
authors.forename: J
authors.initials: J
authors.lastname: Ring
authors.forename: T
authors.initials: T
authors.lastname: Illig
mesh_terms: D053818:Chymases; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics*; D012882:Skin Tests; D011795:Surveys and Questionnaires
chemical_list: D007073:Immunoglobulin E; D012697:Serine Endopeptidases; C509226:CMA1 protein, human; D053818:Chymases