A novel polymorphism in the cytoplasmic region of the human immunoglobulin A Fc receptor gene*

Abstract

The Fc receptor for immunoglobulin A (IgA), FcalphaRI, is expressed on several types of myeloid cells, and activates them upon ligand binding. However, binding of IgA to the extracellular domain of the receptor requires previous stimulation of the cell by cytokines, and the cytoplasmic tail of FcalphaRI has been shown to play a role in this. Therefore, polymorphism in this region might affect this process. However, no changes in the amino acid sequence in this region of the FcalphaRI have so far been reported. Here, we describe for the first time a single nucleotide polymorphism in exon 5 of the immunoglobulin A Fc receptor (FCAR) gene leading to a Ser-->Gly substitution at position 248 of the mature FcalphaRI protein. Prediction of structural features suggests some changes that may affect the function of the protein to some extent. However, the Gly248 variant is quite common (4% homozygotes and 38% heterozygotes) in healthy population, suggesting a weak effect, if any, on function, at least in heterozygotes.

FcαRI (CD89) Alleles Determine the Proinflammatory Potential of Serum IgA

“…As part of an effort to understand the role of naturally occurring polymorphisms in Ig receptors, we sequenced the entire coding region of Fc␣RI from a large number of donors and confirmed a common nonsynonymous SNP (SNP 844A3 G) within the Fc␣RI CYT domain (39). Using this natural sequence variation as a biological probe, we have demonstrated that the two different alleles of the CYT domain of CD89 ␣-chain alter receptor signaling and its biological functions.…”

Fc Receptors in Mucosal Immunology

“…Three SNPs lie in the promoter and one of these has been reported to be associated with an increased disposition to IgA nephropathy (IgAN) (Tsuge et al, 2001;Jasek et al, 2004), although this association was not seen in another study (Narita et al, 2001). These SNPs may also have an impact on the risk for chronic hepatitis C (Watanabe et al, 2006).…”

Human FcR Polymorphism and Disease

“…FCAR (CD89) encodes the human IgA receptor FcαRI. A common SNP (844A > G) was identified through direct sequencing of the coding region of FCAR (CD89) (Jasek et al 2004 ; Wu et al 2007 ). This transition changes amino acid codon 248 in the cytoplasmic domain from serine to glycine, resulting in enhanced cellular functions.…”