Background HLA-DR (DRB1*15 and DRB1*03) component is weakly associated to SLE and other genes and genetic regions are investigated in order to better characterise the genetic predisposition to the disease. DMA and DMB genes are located within the HLA class II region. The alpha beta heterodimer encoded by these genes is directly involved in the HLA class II-restricted antigen presentation pathway. Limited nucleotide polymorphism has been described in the 3rd exon of the DMA and DMB genes.
Objectives To look for an association between DM polymorphism and SLE, the DMA and DMB allele distribution was compared between patients and controls from the same geographic area.
Methods 73 SLE patients were selected according the 1997 ACR criteria. 147 unrelated control individuals were randomly selected (random controls: RC). A second group of 88 unrelated controls who were closely matched for DRB1 genotypes with patients was defined (matched controls: MC) in order to determine whether the association between SLE and certain DM alleles resulted from direct influence of the DM genes or indirect influence through linkage disequilibrium with alleles at the DRB1 locus. All the individuals were typed for DR and DM by SSOs after genomic DNA extraction of peripheral mononuclear cells and PCR. The significance of differences in phenotype frequencies was determined by Fischer’s exact tests with Bonferoni correction.
Results 49.3% of the patients carry either DRB1*15/16 (21.9%) or DRB1*03 alleles (27.4%), or both. DMA*0103, DMA*0104 and DMB*0102 were found to be more frequent in SLE patients compared to RC (p = 0.0012, p = 0.0012, p = 0.0097, respectively). Similarly the frequency of these alleles was increased in patients compared to MC (p = 0.0058, p = 0.0013, p = 0.017, respectively) suggesting a direct influence of DM genes on SLE susceptibility. This direct influence was confirmed by showing no significant difference of DM allele frequencies between RC and MC. Finally, after stratification of the patients and the MC according to the DRB1 genotypes, DMA*0104 was increased in DRB1*15/16, DRB1*03 negative patients.
Conclusion These data show an association between SLE susceptibility and DMA*0103, *0104, DMB*0102. The influence of these alleles cannot be explained by linkage disequilibrium with SLE-associated alleles.