title: Rheumatoid arthritis.
abstract: The results of family and twin studies suggest that RA may result from an interaction between an oligogenic susceptibility and unknown environmental factors. Part of this genetic predisposition is accounted for by genes within the MHC where there is a well-documented association with HLA-DR4. Studies of DR and other MHC variants have shown different associations with particular subgroups. One subgroup is Felty's syndrome where there is a strong association with DR4, as well as associations with DQ-beta and C4B null variants when DR4-matched Felty's and RA subjects are analysed. These DQ-beta and C4B null variants may characterize a single haplotype which is associated with extra-articular disease. A further rheumatoid subgroup characterized by circulating antibodies to native type II collagen, shows an association with HLA-DR3 and 7. Genes on chromosome 14 may also influence susceptibility to RA, probably by interaction with MHC genes and there are different Gm associations for DR4-positive and collagen-antibody-positive rheumatoid subgroups. HLA and Gm markers so far identified only account for a small part of the total genetic predisposition to RA and a third or further loci may also be involved. Possible candidates include T-cell alpha- and beta-chain genes and immunoglobulin light chain genes. One present concept of the genetic predisposition to RA is of several independent immunogenetic pathways each including interactions at two or more loci.
authors.forename: D M
authors.initials: DM
authors.lastname: Grennan
authors.forename: P A
authors.initials: PA
authors.lastname: Sanders
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D004198:Disease Susceptibility; D004200:Diseases in Twins; D008040:Genetic Linkage; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D010375:Pedigree
chemical_list: D006684:HLA-DR Antigens