Genetics of HLA-associated disease; rheumatoid arthritis

An association between rheumatoid arthritis (RA) and the HLA antigen DR4 supports the view that genes in the HLA region are important in susceptibility to this disease. To further define the basis for genetic susceptibility to RA, we analyzed HLA haplotype sharing among affected and unaffected individuals in 29 multiple-case families with definite or classic RA. We have observed a non-random distribution of HLA haplotypes to unaffected as compared with affected offspring in sibships containing two or more affected individuals having 3 of 4 parental haplotypes. These data support the view that susceptibility to RA is determined, at least in part, by genes in the HLA region of chromosome 6.