Gene Variants Predicts Rheumatoid Arthritis Disease Outcomes

Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response.

Certain genetic variants are associated with higher or lower risks of increased disease severity and a new way has been identified in which genotyping can be used to predict disease outcomes among sufferers of rheumatoid arthritis (RA).

Scientists at the University of Manchester (UK) and their colleagues from other institutions analyzed data from three independent multicenter prospective cohort studies, including a total of nearly 4,000 patients in total. Longitudinal statistical modeling was performed to integrate multiple radiograph records per patient over time. All patients were from the UK and had self-reported white ancestry.

All samples available in 2010 from two of the cohorts with a diagnosis of RA and of sufficient DNA quality were genotyped using a single-nucleotide polymorphism microarray Infinium Immunochip (Illumina; San Diego, CA, USA) and imputed at the amino acid resolution. The human leukocyte antigen (HLA) typing was performed using a semi-automated, reverse dot-blot method.

The scientists found that the amino acid valine at position 11 of the Major Histocompatibility Complex, Class II, DR Beta 1 (HLA-DRB1) gene was the strongest independent genetic determinant of radiological damage in rheumatoid arthritis. Moreover, it was revealed that positions 71 and 74 represented independent predictors, with the three positions together—11, 71, and 74—strongly associated with disease outcomes. It was also revealed that HLA-DRB1 haplotypes associated with rheumatoid arthritis susceptibility and severe outcomes were also predictors of good treatment response with anti-tumor necrosis factor (TNF) therapy, an important class of biological drugs.

Stephen Simpson, PhD, a director at Arthritis Research UK (Chesterfield, UK), said, “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. This new study takes us a step closer to that goal.” The study was published on April 28, 2015, in the Journal of the American Medical Association (JAMA).

Related Links:
University of Manchester 
Illumina 
Arthritis Research UK