Investigating the genetic basis of susceptibility to rheumatoid arthritis.

The challenges in identifying genetic polymorphisms that influence the susceptibility to rheumatoid arthritis are the same as those faced in most complex diseases; genetic and phenotypic heterogeneity, an unknown number of loci presumed to have small genetic effects, non-genetic modifying effects that have yet to be fully characterised and a history of unconfirmed genetic associations. Despite the difficulties, the chronic nature of the disease, incomplete efficacy of existing therapies and resultant heavy healthcare burden for the developed world in managing patients with this condition, mean that an understanding of the genetic basis of disease susceptibility, severity and response to therapy is keenly sought. Many linkage and association studies have been carried out and in this article the results of linkage studies are summarised. Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, CTLA-4 and MIF.