ABSTRACT
Genetic susceptibility A genetic association is suggested by the fact that RA is more common in firstdegree relatives of patients than in the population at large; furthermore twin studies have revealed a concordance rate of around 30 per cent if one of the pair is affected. The human leucocyte antigen (HLA) DR4 occurs in about 70 per cent of people with RA, compared to a frequency of less than 30 per cent in normal controls. HLA-DR4 is encoded in the major histocompatibility complex (MHC) region on chromosome 6. There are strong associations between HLA-DR4 and RA. In particular a key structural conformation within the HLA-DR4 binding groove called the ‘shared epitope’ seems important. This may suggest that a particular antigen that fits into this may be playing a part.
