A comparative search for human FcεRIα gene (FCER1A) 3′-UTR polymorphisms in Japanese and Polish populations

Abstract

The high affinity immunoglobulin E (IgE) receptor (FcεRI) plays a key role in the pathogenesis of atopy and allergic disorders. Several polymorphisms located in 5'-flanking region and 5'-untranslated region (5'-UTR) of human FCER1A, the gene encoding FcεRI α-subunit, have been shown to functionally affect its transcriptional activity. All those genetic variants have been also associated with allergic diseases and/or serum IgE levels. In the present study, we sought to identify functional polymorphisms in human FCER1A 3'-untranslated region (3'-UTR), the potential candidates for future genetic association studies. Search for polymorphisms within human FCER1A 3'-UTR region, conducted in Japanese and Poles, revealed the presence of +5650A>G and +5714G>A variants. Subsequently, structure/distribution of haplotypes and LD measures were analyzed in Japanese and Poles for both 3'-UTR variants and the functional polymorphisms located in 5'-flanking region and 5'-UTR of human FCER1A. Additionally, reporter plasmids containing human FCER1A main promoter and 3'-UTR with all four possible combinations of +5650A>G and +5714G>A polymorphisms were constructed to evaluate functional potential of both 3'-UTR variants. However, no genotype-related differences in the gene expression were observed, as measured by reporter activity in cultured human basophil/mast cell-like KU812 cells, suggesting that both +5650A>G and +5714G>A have no genotype-related functional effect. In summary, we described linkage disequilibrium and the distribution of haplotypes for two identified human FCER1A 3'-UTR polymorphisms and several previously reported 5'-flanking region and 5'-UTR variants in Japanese and Poles, representative for East Asians and Caucasians, the two ethnic groups in which genetic associations between FCER1A and allergic diseases and/or serum IgE levels have been previously reported.