Scientists from University of North Carolina at Chapel Hill School of
Medicine and Interleukin Genetics Inc. recently announced findings from a large
clinical study to evaluate the role played by genetic factors in the worsening
of osteoarthritis (OA).
The study, which was part of the Johnston County Osteoarthritis Project,
showed patients with X-ray evidence of knee OA 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 as other patients.
Results from the study, which followed 1,154 patients for as long as 11 years,
were presented at the World Congress on Osteoarthritis in Brussels, Belgium.
The study, led by Joanne Jordan, MD, MPH, the Herman & Louise Smith
Distinguished Professor of Medicine and chief of the Division of Rheumatology,
Allergy, and Immunology at the Thurston Arthritis Research Center at University
of North Carolina at Chapel Hill, is the first of its kind to include both
African-Americans and Caucasians, as well as inclusion of genetic,
radiographic, serologic, physical and functional examinations of its
“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,”
Jordan stated in a press release.
Interleukin Genetics previously reported that variations in the gene for
IL-1Ra are strongly associated with severe knee OA and this clinical study
validates the company’s earlier findings and other previous studies that
have implicated the anti-inflammatory protein IL-1Ra in progression to severe
“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,” Ken Kornman, chief scientific officer for
Interleukin Genetics, stated. “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.”
Participants at the start of the Project were analyzed for genetic
markers that predicted those subjects who remained stable and those subjects
who progressed to severe OA, as measured in X-rays. Nine genes were found to be
associated with OA progression, with the strongest prediction of progression
from combinations of gene variations in the gene for IL-1Ra.
Interleukin-1 is one of the key chemicals involved in cartilage and bone
destruction, and on specific genetic patterns in the naturally occurring
inhibitors of that are predictive of Interleukin-1 and of OA progression. The
study 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.