HLA DMA and DMB show no association with rheumatoid arthritis in US Caucasians

HLA DM is a heterodimeric molecule functioning in normal antigen presentation; it is encoded by adjacent HLA-region loci, HLA DMA and DMB, located between DP and DQ. Some previous studies have suggested that HLA susceptibility to rheumatoid arthritis (RA) is associated with certain DMA and DMB alleles. Our aim was to examine whether this association is also present in US Caucasians. We studied 288 US Caucasian subjects with rheumatoid arthritis and 263 US Caucasian control subjects. DMA and DMB typing was achieved by PCR amplification followed by sequence-specific oligonucleotide hybridization and by PCR-restriction fragment length polymorphism. There was no frequency difference for DMA alleles or DMB alleles between RA and control subjects, indicating no association. Neither was a difference apparent when data were analysed in subgroups based on shared-epitope DRB1, on the rheumatoid factor test, on radiographic changes of RA, or on sex. DRB1-DQB1-DMB analyses for linkage disequilibrium showed that the DRB1*0401-DQB1*0301 haplotype had the DMB*0103 allele more often than DMB*0101 (estimated haplotype frequencies 0.08 and 0.039 in RA, respectively). In contrast, the DRB1 *0401-DQB1 *0302 haplotype usually had the DMB*0101 allele (haplotype frequency 0.084 compared to 0.01 for DMB*0103). Thus, neither HLA DMA nor DMB was associated with RA in this population, and not all shared-epitope-bearing haplotypes had the same DMB allele distribution.