Gene Placement on Chromosome Influences Rheumatoid Arthritis Disease Onset, Severity, and Mortality

There are genetic risk factors that account for rheumatoid arthritis (RA) severity, as well as the risks of death and response to treatment, according to research published in JAMA.

Researchers from the University of Manchester in England led by Anne Barton, PhD, FRCP studied patients from the Norfolk Arthritis Register and the Early RA Study to assess whether the gene HLA-DRB1 and its set of DNA (haplotypes) were linked to RA susceptibility, death, and response to medications (such as tumor necrosis factor TNF inhibitor drugs).

There were 2,112 patients used to evaluate radiologic severity, 2,432 patients used in the mortality analysis, and 1,846 patients used to examine treatment response to TNF inhibitor medication.

The authors noted that previous research has made advancements in identifying genetic susceptibility loci (the specific site of a particular gene on its chromosome) in autoimmune diseases; however, more evidence is needed to support the loci’s link to disease prognosis and treatment response.

“Among patients with RA, the HLA-DRB1 locus, which is associated with disease susceptibility, was also associated with radiological severity, mortality, and treatment response,” the authors concluded. “Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRB1 haplotype analysis for management of RA.”

In an accompanying editorial, David T. Felson, MD, MPH, from Boston University School of Medicine and Lars Klareskog, MD, PhD, from the Karolinska Intitutet in Stockholm, Sweden wrote that these findings are important for 3 particular reasons. First, the authors of the editorial wrote, the findings may add to the ability to predict RA outcomes. By doing so, therapeutic strategies can be optimized and personalized for individual patients. Second, they continued, these findings can shed light on the molecular mechanisms that determine disease course and mortality. The third reason the editorial authors believe this findings are important is because the results can help inform understanding of disease pathogenesis. The results implicate HLA-DRB1 immune events for disease prognosis and mortality, as well as onset of RA.

The editorial authors continued by saying that these findings may not change clinical practice immediately, but determining HLA-DRB1 influences disease prognosis is definitely of interest. Felson and Klareskog additionally believe that these observations can influence future research, including replications of this investigation. These findings can impact future studies on the determinants of disease progression and development for various diseases including RA.