Endocrine Abstracts

Autoimmune diseases (AIDs) have been shown to share a series of genetic susceptibility loci, including the HLA class II region, CTLA-4 and PTPN22, indicating the sharing of key pathways between diseases. Recently, the rs1801274 single nucleotide polymorphism (SNP) within the Fc gamma receptor 2a gene (FcGR2a) has been shown to be associated with several common AIDs including type 1 diabetes, rheumatoid arthritis and coeliac disease. FcGR2a is an immune modulator found on the surface of T-cells, macrophages and natural killer cells and is involved in the destruction of autoantibodies, which are present in all AIDs, suggesting that disruption in this molecule could play a role in disease onset/progression. To determine if FcGR2a also contributes to Graves’ disease (GD) susceptibility, nine Tag SNPs, including rs1801274, were used to screen all the common variation within FcGR2a in a large UK Caucasian data set comprising of 2504 GD patients and 2784 geographically matched controls. All subjects gave informed written consent, and the project was approved by the local ethics committee. Association of rs1801274 (P=0.003, OR=1.13) and a further SNP rs6427598 (P=0.012, OR=1.12) was detected. Four other SNPs showed no association with GD, with three other SNPs not adhering to HWE and these were, therefore, excluded from further analysis. FcGR2a haplotype analysis identified one haplotype block consisting of rs4656308-rs1801274 (P=0.003, OR =1.13), although the association detected was similar to that of the rs1801274 SNP alone. None of the SNPs showed any correlations with specific phenotypic manifestations of GD. This study provides further evidence to suggest that alteration in autoantibody clearance could be a mechanism in the onset of autoimmunity and a potential new target for therapeutic intervention. Further work is now required on this region in both GD and other AIDs to confirm the role of FcGR2a in disease susceptibility.