Modeling the HLA component in rheumatoid arthritis: Sensitivity to DRB1 allele frequencies

Rheumatoid arthritis is an inflammatory disease for which positive associat ions have been described with some HLA-DRB1 alleles. The associated alleles share a similar amino acid sequence in the third hypervariable region, the shared epitope, but differ at position 71 and 86. It has been suggested th at HLA susceptibility to rheumatoid arthritis could be due not only to the shared epitope hut could also be influenced by specific amino acids at posi tions 71 and 86. In this study, we investigated the role of these amino aci ds in rheumatoid arthritis on 203 unrelated patients. An involvement of ami no acid 71 was detected but no conclusion was possible regarding amino acid 86. A study of the sensitivity of the conclusions to marker allele frequen cies was performed. We showed that the results obtained for amino acid 71 a re not very sensitive to allele frequencies but those obtained at position 86 are highly sensitive. This emphasizes the importance of studying the rob ustness of results: to variations in allele frequencies before conclusions are drawn. (C) 2000 Wiley-Liss, Inc.