Genetic Haplotypes Correlate with RA Severity, According To Study

Genetic Haplotypes Correlate with RA Severity, According To Study

Knowing if you will be affected by severe rheumatoid arthritis even before you attempt treatment may be possible using the results of a study conducted at University of Manchester. Lead author Dr. Sebastien Viatte, part of the Arthritis Research UK Centre for Genetics and Genomics at the university, described how genetic variants are associated with rheumatoid arthritis disease severity in the article, “Association of HLA-DRB1 Haplotypes With Rheumatoid Arthritis Severity, Mortality, and Treatment Response,” which was published in the Journal of the American Medical Association (JAMA).

“This major advance in genetics might allow stratification of rheumatoid arthritis patients at the onset of their disease to identify those at risk of joint damage and early death, and also those who are more likely to respond to anti-tumor necrosis factor (TNF) biological therapy,” said Dr. Viatte in a news release from the university. This would allow patients and their physicians to work together to tailor treatment specifically to the patients’ needs, allowing for a maximally beneficial response to treatment.

The study was conducted at multiple centers with patients found in the Norfolk Arthritis Register, in which there are 1691 patients and 2811 radiographs available for data analysis. The goal, according to the publication, was, “To assess whether specific HLA-DRB1 haplotypes associated with rheumatoid arthritis susceptibility are also associated with radiological severity, mortality, and response to TNF inhibitor drugs.” The researchers studied 16 HLA-DRB1 haplotypes, or closely-linked, inherited DNA variations.

Results identified that having a valine amino acid at position 11 of the HLA-DRB1 gene was highly predictive of radiological damage in patients with rheumatoid arthritis. Positions 71 and 74 were also strongly predictive, and all three positions were significantly associated with a more severe outcome of disease. Fortunately, these haplotypes were also predictive of a strong response to anti-TNF therapy.

“To treat patients with rheumatoid arthritis more effectively and to prevent them being given drugs which won’t work for them, it’s important to know who is most likely to respond best to which drug, when and at what dose,” commented Dr. Stephen Simpson, director of research at Arthritis Research UK. “This new research takes us a step closer to that goal.” The authors note that additional measures in reaching this goal include validating the study’s findings in other patient subsets.

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