Positive association of the HLA DMB1*0101-0101 genotype with rheumatoid arthritis

Abstract

Objective. HLA DM is a non-classical major histocompatibility complex (MHC) class II molecule that has been shown to facilitate peptide loading with classical class II molecules. Methods. In this study, we analysed the polymorphism in exon 3 of HLA DMA and DMB genes by a polymerase chain reaction-sequence-specific oligonucleotide probe method in 163 rheumatoid arthritis (RA) patients and 146 ethnically matched controls. The HLA-DRB1 genotype was also analysed by a reverse-dot blot method. Results. Our results show in RA patients a significant increase in the HLA DMB*0101 allele frequency (83% vs 72.3% of the controls, P < 1.6 x 10-3, significance at P < 0.0125) and in the HLA DMB*0101-0101 homozygote genotype frequency [70.8% vs 50% of the controls, P < 4.2 x 10-4, significance at P < 0.00625, odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.43-4]. The increase in DMB*0101 allele and homozygote genotype frequencies was independent of a linkage disequilibrium between DMB and DRB1 alleles. The analysis of non-random associations between the HLA-DM and DRB1 alleles only revealed a significant association in controls between DMB*0104 and DRB1*07 alleles (Δ = 0.01, P < 7 x 10-4, significance at P < 9.6 x 10-4). On the other hand, the DMB*0101-0102 genotype frequency was increased in DRB1*0401-negative RA patients as compared to controls (11% vs 2%, P < 0.011, significance at P < 0.015, OR = 6.2, 95% CI: 1.2-30). Conclusion. Our data suggest that HLA-DM alleles could play a role in the genetic susceptibility to RA.