University of Minnesota
University Relations
http://www.umn.edu/urelate
612-624-6868

Minnesota Supercomputing Institute


Log out of MyMSI
WuJ

Research Abstracts Online
January - December 2011

Main TOC ...... Next Abstract

University of Minnesota Twin Cities
College of Veterinary Medicine
Department of Veterinary and Biomedical Sciences

PI: Jianming Wu

Function of FcγRIIC Gene in Rheumatoid Arthritis

Functionally significant single nucleotide polymorphisms (SNPs) in human IgG Fc receptor (FcγR) genes play important roles in modulating the immune system and in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). Within a classical Fcγ receptor gene cluster, human FcγRIIC (FCGR2C or CD32C) encodes an activating Fcγ receptor. FcγRIIC has been largely ignored because of a translation termination codon in the first extracellular domain. These researchers have discovered that a non-synonymous coding region SNP in FcγRIIC (SNP 202T>C) not only changes the translation termination codon (TAG, STP allele) to a glutamine codon (CAG, ORF allele) but also enables the expression of a functional activating FcγRIIC on human B cells. Such expression completely changes the paradigm of FcγR regulation of B cells from un-opposed inhibition in 202T individuals to activation in 202C individuals. They have also identified two novel SNPs in the FcγRIIC intron 6, both of which alter conserved splicing motifs. Disruption of canonical splicing signals typically leads to a defect in pre-mRNA splicing, and thus these intron 6 SNPs may generate the altered FcγRIIC mRNA isoforms and protein products. Because B cells are obligatory cells for the production of pathogenic antibodies in RA patients, the researchers hypothesize that the shift of expression from the un-opposed FcγRIIB to the activating FcγRIIC on B cells will promote the production of rheumatoid factor and anti-CCP antibodies and that FcγRIIC SNPs are risk factors for RA or subsets of RA.

Group Member

Rui Lin, Research Associate