Are Single Nucleotide Polymorphisms of the <i>Immunoglobulin A Fc Receptor</i> Gene Associated with Allergic Asthma?

Abstract

Background: Eosinophils are important components of allergic inflammation. The immunoglobulin A (IgA) Fc receptor (FcαRI), encoded by the FCAR gene, is a possible candidate for eosinophil activation at mucosal surfaces, where IgA is abundant. Both elevated cell surface expression of FcαRI and increased avidity for IgA were described on eosinophils from allergic subjects. The aim of our study was to examine the possible association of FCAR gene polymorphisms with allergic asthma. Methods: We screened three regions of the FCAR gene: (1) the promoter region, (2) exon 3, encoding the first extracellular domain (EC1), and (3) exon 5, coding for the transmembrane and cytoplasmic domain, for new and published polymorphisms using a sensitive temperature gradient gel electrophoresis technique and compared their frequencies in 112 patients diagnosed with allergic asthma and 100 healthy controls. Results: Six polymorphisms, including two novel ones, were detected. No differences between patients and controls were found in the distribution of any of these polymorphisms. Conclusion: FcαRI polymorphism does not seem to be a risk factor in allergic asthma. Nevertheless, this is the first report on the distribution of 6 single nucleotide polymorphisms of the FCAR gene in a human population and the first study on FCAR polymorphism in allergic asthma.

The function of immunoglobulin A in immunity

“…However, since the transition results in no change in amino acid sequence, the possibility that the differential susceptibility could be explained by another gene polymorphism located near the FcαRI D1 domain cannot be ruled out. No association with any polymorphism was found when all six polymorphisms were screened in allergic asthma patients and controls 44.…”

“…Polymorphisms in some classes of Fc receptor have been associated with increased susceptibility to certain diseases. There are three known polymorphisms in the FcαRI promoter region, one of which is reportedly associated with an increased disposition to IgA nephropathy 43, 44. Single nucleotide polymorphisms have also been documented in the coding region of the gene, two in D1 and a third in the cytoplasmic tail.…”

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

“…The effect of this variation on IgA binding is not known, although it is located closely to the ligand binding site. 52 Finally, a functional SNP has been identified in the intracellular domain (844A / G), which results in an aa transition from serine to glycine (S248 -G248). 50 IgA-mediated crosslinking of neutrophil Fc RI -G248 triggered significantly more interleukin (IL)-6 release than equivalent crosslinking of the Fc RI -S248 variant.…”

Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

“…Studies conducted by Sauzeau et al [126], Xu et al [127], Hirota et al [128], Alharatani et al [129], Beitelshees et al [130], Zhu et al [131], Gil-Cayuela et al [132], Liu et al [133], Xie et al [134], Kroupis et al [135], López-Mejías et al [136], Gremmel et al [137], Yamada and Guo [138], Petri et al [139], DeFilippis et al [140], Rocca et al [141] and Tur et al [142] indicated that of VAV2, RASAL1, LIF (LIF interleukin 6 family cytokine), CTNND1, CACNA1C, MAP3K10, NRBP2, TRPM4, LILRB2, FCGR2A, PIK3CG, SELPLG (selectin P ligand), PRDX4, FPR2, PLG (plasminogen), SELENOM (selenoprotein M) and NCAM1were associated with cardiovascular diseases, but these genes might be responsible for progression of obesity associated type 2 diabetes mellitus. Previous studies indicated that ITGB4 [143], SEMA3D [144], FCAR (Fc fragment of IgA receptor) [145], KIT (KIT proto-oncogene, receptor tyrosine kinase) [146], PGLYRP1 [147], IL17RB [148], BIRC5 [149] and PTGS1 [150] plays an important role in asthma, but these genes might be linked with progression of obesity associated type 2 diabetes mellitus. GRK2 [151], ADCY3 [152], FASN (fatty acid synthase) [153], DGKD (diacylglycerol kinase delta) [154], DGKQ (diacylglycerol kinase theta) [154], IP6K1 [155], ANXA1 [156], SUCNR1 [157], PRNP (prion protein) [158], CXCR4 [159], CAV1 [160], LCN2 [161], AQP9 [162], NMU (neuromedin U) [163], NPY1R [164], FFAR2 [165], OSM (oncostatin M) [166] and TREM1 [167] were reported in obesity associated type 2 diabetes mellitus.…”