Association of Fc receptor like 5 (FCRL5) with Graves' disease is secondary to the effect of FCRL3

Matthew J Simmonds (1) , Oliver Brand (1) , Jeffrey Barrett (2) , Paul Roger Newby (3) , Jayne A Franklyn (3) , Stephen Gough (1)

1 OCDEM - Oxford Centre for Diabetes, Endocrinology and Metabolism
2 The Wellcome Trust Sanger Institute [Cambridge]
3 Medical and Dental Sciences

Abstract (Words = 235 [250 maximum]) Objective: The Fc receptor like 3 (FCRL3) molecule, involved in controlling B cell signalling, may contribute to the autoimmune disease process. Recently a genome wide screen detected association of neighbouring gene FCRL5 with Graves' disease (GD). To determine whether FCRL5 represents a further independent B cell signaling GD susceptibility loci we screened 12 tag SNPs, capturing all known common variation within FCRL5, in 5192 UK Caucasian GD index cases and controls. Design: A case control association study investigating twelve tag SNPs within FCRL5 which captured the majority of known common variation within this gene region. Patients: A dataset comprising 2504 UK Caucasian GD patients and 2688 geographically matched controls taken from the 1958 British Birth cohort. Measurements: We used the chi-squared test and haplotype analysis to investigate association between the tag SNPs and GD before performing regression analysis to determine if association at FCRL5 was independent of the known FCRL3 association. Results: Three of the FCRL5 tag SNPs, rs6667109, rs3811035 and rs6692977 showed association with GD (P=0.015-0.001, OR=1.15-1.16). Logistic regression performed on all FCRL5 and, previously screened, FCRL3 tag SNPs revealed that association with FCRL5 was secondary to linkage disequilibrium with the FCRL3, rs11264798 and rs10489678 SNPs. Conclusions: FCRL5 does not appear to be exerting an independent effect on the development of GD in the UK. Fine mapping of the entire FCRL region is required to determine the exact location of the etiological variant/s present.

Mots clés: Medicine

Matthew J Simmonds, Oliver Brand, Jeffrey Barrett, Paul Roger Newby, Jayne A Franklyn, et al.. Association of Fc receptor like 5 (FCRL5) with Graves' disease is secondary to the effect of FCRL3. Clinical Endocrinology, 2010, 73 (5), pp.654. ⟨10.1111/j.1365-2265.2010.03843.x⟩. ⟨hal-00553273⟩