Recently, linkage between chromosome 1q23 and rheumatoid arthritis within the Japanese population has been narrowed down to association of four single nucleotide polymorphisms (SNPs), fcrl3_3, fcrl3_4, fcrl3_5 and fcrl3_6, within FCRL3, a known regulator of B cell signalling. Of these four SNPs, fcrl3_3 was shown to disrupt FCRL3 expression on B cells, suggesting a potential etiological role. Association of fcrl3_3 was also replicated in a Japanese Graves disease (GD) cohort. The aim of this study was to investigate these four FCRL3 SNPs within a large UK Caucasian GD dataset. In total 1056 patients with GD and 864 control subjects were genotyped for each SNP. All subjects gave informed written consent, and the project was approved by the local ethics committee. Association was found between GD and fcrl3_3 (OR =1.19, 95% CI =1.031.37), fcrl3_5 (OR =1.18, 95% CI =1.041.35) & fcrl3_6 (OR =1.20, 95% CI =1.051.36), although at a significantly lower level than previously reported. Only a trend towards significance was detected for fcrl3_4 (P=0.059). No evidence for an interaction with the previously established HLA class II, CTLA-4 and PTPN22 GD-associated alleles was detected for any of these SNPs. Similarly there was no evidence for association with any specific GD sub-phenotype. Linkage disequilibrium (LD) analysis revealed LD between fcrl3_4, fcrl3_5 and fcrl3_6 but not fcrl3_3. Further replication in independent datasets and fine mapping of the surrounding gene regions in UK Caucasians is now needed to confirm the magnitude of the effect and location of the etiological variant(s) present within this gene region.
01 - 05 Apr 2006
European Society of Endocrinology