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A role of FCER 1A and FCER 2 polymorphisms in I g E regulation
Author(s) -
Sharma V.,
Michel S.,
Gaertner V.,
Franke A.,
Vogelberg C.,
Berg A.,
Bufe A.,
Heinzmann A.,
Laub O.,
Rietschel E.,
Simma B.,
Frischer T.,
Genuneit J.,
Potaczek D. P.,
Kabesch M.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12336
Subject(s) - single nucleotide polymorphism , immunoglobulin e , genotype , allele , genome wide association study , snp , population , biology , genetics , haplotype , polymorphism (computer science) , snp genotyping , immunology , gene , medicine , antibody , environmental health
Background Both FCER 2 and FCER 1A encode subunits of IgE receptors. Variants in FCER 1A were previously identified as major determinants of IgE levels in genome‐wide association studies. Methods Here we investigated in detail whether FCER 2 polymorphisms affect IgE levels alone and/or by interaction with FCER 1A polymorphisms. To cover the genetic information of FCER 2 , 21 single‐nucleotide polymorphisms ( SNP s) were genotyped by Illumina HumanHap300 BeadChip (5 SNP s) and the matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry ( MALDI ‐ TOF MS ; 14 SNP s) in at least 1303 Caucasian children (651 asthmatics) ( ISAAC II / MAGICS population); genotypes of two SNP s were imputed. Results SNP rs3760687 showed the most consistent effect on total serum IgE levels (b [ SE ] = −0.38 [0.16]; P = 0.016), while FCER 2 polymorphisms in general were predominantly associated with mildly‐to‐moderately increased IgE levels (50th and 66th percentiles). Gene‐by‐gene interaction analysis suggests that FCER 2 polymorphism rs3760687 influences IgE levels mainly in individuals not homozygous for the risk allele of FCER 1A polymorphism rs2427837, which belongs to the major IgE‐determining tagging bin in the population. Conclusion FCER 2 polymorphism rs3760687 affects moderately elevated total serum IgE levels, especially in the absence of homozygosity for the risk allele of FCER 1A SNP rs2427837.