HLA-DQ beta-chain polymorphism in HLA-DR4 haplotypes associated with rheumatoid arthritis

With a cDNA probe for the DQ beta gene, two variants of the DR4-linked DQw3 (3.1 and 3.2) allele were analysed in patients with rheumatoid arthritis (RA), healthy individuals, and homozygous cell lines. The DQw3.1 allele, identified by 3.4 kb (HindIII), 2.3 kb (SstI), and 3.7 kb and 6.9 kb (BamHI) restriction fragment lengths, was expressed in 100% (of 18) DR4-positive patients, compared with only 19% (of 16) of DR4-positive controls including one of five homozygous cell lines. This DQ beta variant showed a highly significant association (relative risk = 78; p less than 10(-6) with RA and may therefore play an important part in susceptibility to RA.