Mapping of a novel susceptibility gene for rheumatoid arthritis in the telomeric MHC region

Rheumatoid arthritis (RA) is a complex heterogeneous disease with an estimated genetic contribution to of 30-50%. Approximately one third arises from the major histocompatibility complex (MHC) at 6p21.3. The contribution of specific DRB1 alleles encoding the shared epitope has been well described, however, several recent studies have suggested that additional telomeric genetic influences may exist. This region is difficult to study as a result of the presence of strong linkage disequilibrium (LD) within the MHC and high gene density particularly in the central class III region. In this article we review the current data supporting the existence of a non-DRB1 susceptibility gene for rheumatoid arthritis, in particular within the class III region.