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Different FCER 1 A polymorphisms influence I g E levels in asthmatics and non‐asthmatics
Author(s) -
Potaczek Daniel P.,
Michel Sven,
Sharma Vishwas,
Zeilinger Sonja,
Vogelberg Christian,
Berg Andrea,
Bufe Albrecht,
Heinzmann Andrea,
Laub Otto,
Rietschel Ernst,
Simma Burkhard,
Frischer Thomas,
Genuneit Jon,
Illig Thomas,
Kabesch Michael
Publication year - 2013
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12083
Subject(s) - asthma , single nucleotide polymorphism , immunoglobulin e , medicine , immunology , genome wide association study , population , allergy , genotype , genetics , biology , gene , antibody , environmental health
Background Recently, three genome‐wide association studies ( GWAS ) demonstrated FCER 1 A , the gene encoding a ligand‐binding subunit of the high‐affinity I g E receptor, to be a major susceptibility locus for serum I g E 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 FCER 1 A polymorphisms are associated with total serum I g E in the general population and asthmatics specifically. Methods Nineteen polymorphisms were studied in FCER 1 A based on a detailed literature search and a tagging approach. Polymorphisms were genotyped by the Illumina H uman H ap300 C hip (6 polymorphisms) or MALDI ‐ TOF MS (13 polymorphisms) in at least 1303 children (651 asthmatics) derived from the G erman 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 I g E was observed for SNP s 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 I g E in asthmatics (lowest p = 0.003), additional polymorphisms (rs3845625, rs7522607, and rs2427829) demonstrated associations with total serum I g E in asthmatics only (lowest p = 0.01). Conclusions These data suggest that FCER 1 A polymorphisms not only drive I g E levels in the general population but that specific polymorphisms may also influence I g E in association with asthma, suggesting that disease‐specific mechanisms in I g E regulation exist.