Genes Identified in Predicting Progression of Osteoarthritis

A large clinical study evaluating the role of genetic factors in osteoarthritis progression reveals a certain group of osteoarthritis sufferers may be more likely to progress to severe disease than others.

The study was sponsored by Interleukin Genetics Inc. and performed at the Thurnston Arthritis Center at the University of North Carolina at Chapel Hill.

The results revealed that patients with radiographic evidence of knee osteoarthritis who inherited a specific pattern of genetic variations in the interleukin-1 receptor antagonist (IL-1Ra) gene were almost twice as likely to progress to severe disease.

The study followed 1,154 subjects for up to 11 years and demonstrated that three specific genetic patterns commonly found in the osteoarthritis population are strongly predictive of different risks for progression of osteoarthritis once it has been diagnosed. The subjects were monitored closely to evaluate the progression of osteoarthritis. They were analyzed for genetic markers that predicted who would remain stable and who would progress to severe osteoarthritis. The team found nine genes to be associated with osteoarthritis progression from combinations of gene variations in the gene for IL-1Ra.

The research was Led by Dr. Joanne Jordan, the Herman & Louise Simth Distinguished Professor of Medicine and Chief, Division of Rheumatology, Allergy, and Immunology at the Thrunston Arthritis Research Center of the Univeristy of North Carolinas at Chapel Hill. The study, titled, “”Johnsonton County Osteoarthritis Project,” included both African-Americans and Caucasians, and included genetic, radiographic, serologic, physical, and functional examinations.

“The strong association shown in this study between progressive OA and the IL-1Ra gene variations, as well as the body of previous related published research, might suggest that this IL-1Ra genetic information could be tested as a tool to identify high-risk patients for participation in clinical trials for the development of a much-needed disease modifying OA drug,” said Jordan, in a press release.

Previously, Interleukin Genetics reported that variations in the gene for IL-1Ra are strongly associated with severe knee osteoarthritis. The new clinical study supports the company's earlier findings and other previous studies that have implicated the anti-inflammatory protein IL-1Ra in progression to severe disease.

“Drug development for OA has been challenging, in part due to the difficulty of enrolling patients who are likely to exhibit disease progression during the study. There appears to be strong potential to use the IL-1Ra genetic patterns to select for clinical trials patients who are more likely to benefit from an effective drug,” said Dr. Kenneth Kornman, Chief Scientific Officer, Interleukin Genetics, in a press release. "A genetic test also would have strong clinical utility for physicians to better manage patients who will more likely progress to a severe form of the disease and require surgery.”

Interleukin Genetics, Inc. develops and markets a line of genetic tests under the Inherent Health(R) brand. The company has identified and holds patents on genetic patterns that lead to over-production of interleukin-1 (IL-1), one of the key chemicals involved in cartilage and bone destruction, and on specific genetic patterns in the naturally occurring inhibitors that are predictive of IL-1 and of OA progression.