Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 10 P81

SFE2005 Poster Presentations Steroids to include Cushing's (15 abstracts)

Association of an FC receptor-like 3 haplotype with autoimmune Addison’s disease suggests an alternative pathogenic allele at the locus

CJ Owen 1 , JA Eden 1 , CE Jennings 1 , V Wilson 1 , TD Cheetham 2 & SHS Pearce 1


1Institute of Human Genetics, University of Newcastle, Newcastle upon Tyne, United Kingdom , 2Child Health, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom.


The common autoimmune endocrinopathies are caused by susceptibility alleles at several genetic loci including MHC, CTLA4, PTPN22 and probably several others. Many of these susceptibility alleles are shared between several different autoimmune disorders including type 1 diabetes, autoimmune thyroid diseases and rheumatoid arthritis. In recent months a novel susceptibility locus was identified in the 5’ end of the Fc receptor-like 3 (FCRL3) gene in Japanese patients with rheumatoid arthritis, Graves’ disease and SLE. The putative susceptibility allele (FCRL3_3C), at position -169 relative to the transcription start site, was associated with a higher promoter activity and with increased NFκB promoter binding in gel-shift studies, suggesting a direct functional role.

We have examined a 4 marker FCRL3 haplotype, encompassing the markers reported to be associated with autoimmunity, FCRL3_3 to FCRL3_6, in UK subjects with autoimmune Addison’s disease (n=104), Graves’ disease (n=616) and in healthy controls (n=469). Genomic DNA was genotyped using a primer extension-MALDI-TOF assay (Sequenom) or by PCR-RFLP. Analysis was performed using haploview and unphased software.

There was tight linkage disequilibrium between the 4 markers studied with pairwise D’ values of between 0.93 and 1.0. Surprisingly, the putative susceptibility allele, FCRL3_3C, was present in a decreased number, of 37.4% of the Addison’s disease alleles, as compared to 47.8% of the control alleles; p=0.007; odds ratio 1.54 (5–95% 1.13 to 2.10). Alleles of the three other FCRL3 markers were also associated with Addison’s disease with p values ranging from 0.02 to 0.008. The four marker FCRL3 haplotype showed association with Addison’s disease with a global p value of 0.02 (unphased). In contrast, no marker showed association with Graves’ disease. These results confirm that FCRL3 is an autoimmune disease susceptibility locus in Caucasians too, but suggest the “disease” allele is other than the promoter -169 FCRL3_3C.

Volume 10

196th Meeting of the Society for Endocrinology and Society for Endocrinology joint Endocrinology and Diabetes Day

Society for Endocrinology 

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