Ann Morgan, from the University of Leeds, and colleagues from other institutions in the UK studied the frequency of various FCGR haplotypes in a group of UK Caucasians (147 RA patients and 127 healthy individuals acting as controls). Dr Morgan is an Arthritis Research Campaign 'Clinician Scientist Fellow'.
One specific FCGR3A-FCGR3B haplotype was found in 31% of RA patients and in 37% of RA patients with a more severe type of RA characterised by lumps around the joints, or nodules. Individuals with 2 copies of this haplotype (homozygous) are three times more likely to develop RA. Homozygous individuals who also have certain variants of human leukocyte antigen (HLA)-DRB1 alleles encoding the 'shared epitope' protein sequence (SE positive), a known risk factor for RA, have a 10 times higher risk of developing RA than SE negative individuals with other FCGR3 variants.
The Fc gamma receptors play important roles in the initiation and regulation of many immunological and inflammatory processes. They also have the ability to bind RA-associated antibodies. This might explain their role in RA pathogenesis.
Article: Analysis of Fcg Receptor haplotypes in rheumatoid arthritis. FCGR3A remains a major susceptibility gene at this locus with an additional contribution from FCGR3B Ann W Morgan, Jennifer H Barrett, Bridget Griffiths, Deepak Subramanian, Jim I Robinson, Viki H Keyte, Manir Ali, Elizabeth A Jones, Robert W Old, Frederique Ponchel, Arthur W Boylston, R DEVA Situnayake, Alexander F Markham, Paul Emery and John D Isaacs Arthritis Research & Therapy, 2005 8:R5