期刊
ALLERGY
卷 69, 期 2, 页码 231-236出版社
WILEY
DOI: 10.1111/all.12336
关键词
FCER1A; FCER2; fine mapping; genetic variants; IgE
资金
- German Ministry of Education and Research (BMBF) as part of the National Genome Research Network (NGFN) [NGFN 01GS0810]
- German Research Council (DFG) [SFB587]
- Deutscher Akademischer Austauschdienst (DAAD) [A/09/74779]
BackgroundBoth FCER2 and FCER1A encode subunits of IgE receptors. Variants in FCER1A were previously identified as major determinants of IgE levels in genome-wide association studies. MethodsHere we investigated in detail whether FCER2 polymorphisms affect IgE levels alone and/or by interaction with FCER1A polymorphisms. To cover the genetic information of FCER2, 21 single-nucleotide polymorphisms (SNPs) were genotyped by Illumina HumanHap300 BeadChip (5 SNPs) and the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS; 14 SNPs) in at least 1303 Caucasian children (651 asthmatics) (ISAAC II/ MAGICS population); genotypes of two SNPs were imputed. ResultsSNP rs3760687 showed the most consistent effect on total serum IgE levels (b [SE]=-0.38 [0.16]; P=0.016), while FCER2 polymorphisms in general were predominantly associated with mildly-to-moderately increased IgE levels (50th and 66th percentiles). Gene-by-gene interaction analysis suggests that FCER2 polymorphism rs3760687 influences IgE levels mainly in individuals not homozygous for the risk allele of FCER1A polymorphism rs2427837, which belongs to the major IgE-determining tagging bin in the population. ConclusionFCER2 polymorphism rs3760687 affects moderately elevated total serum IgE levels, especially in the absence of homozygosity for the risk allele of FCER1A SNP rs2427837.
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