Valine at position 11 of the HLA-DRB1 gene was shown to be the strongest independent genetic determinant of radiological damage in rheumatoid arthritis (RA) in addition to positions 71 and 74, researchers presented at the European League Against Rheumatism Annual Congress (EULAR 2014).
Earlier research had shown a group of alleles on the HLA-DRB1 gene (“shared epitope”) was thought to have the strongest effect on RA susceptibility. Scientists conducted 3 multicenter, prospective cohort studies: the Norfolk Arthritis Register-NOAR (n=1691); the Early Rheumatoid Arthritis Study-ERAS (n=421); and a cohort from 57 UK centers-BRAGGSS (n=1846) to assess whether HLA-DRB1 positions 11, 71, 74 could predict radiological outcome, anti-TNF response, and mortality.
Researchers concluded that the 3 positions together, 11, 71, and 74, which define a total of 16 haplotypes, were strongly associated with disease outcomes. Further, the range of risk to protective effects also matched up with that observed for disease susceptibility. The haplotypes associated with RA susceptibility and severe outcome were also predictors of good anti-TNF therapy treatment response as well as both all-cause and cardiovascular mortality.
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