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The evolution of knee osteoarthritis can be predicted by a clinically validated genetic test

14 Jan 2015
  • The scientific journal Rheumatology has published the results of the clinical trial from which scientists have developed Arthrotest™, the first diagnostic test for joint health
  • The study identified eight genetic polymorphisms and a clinical variant that are significantly associated with rapidly progressing knee osteoarthritis
  • This new tool allows one to detect the worst prognostic patients that are at elevated risk of needing prosthetic knee surgery within a short amount of time

The scientific journal Rheumatology has published online the results of the Arthrotest study, a multicenter clinical trial lasting four years that involved 282 knee osteoarthritis patients and 31 Spanish healthcare centers, as well as medical professionals from different fields.
The study has identified eight hereditary genetic variants as well as one clinical variant that are significantly associated with the rapid progression of knee osteoarthritis. The combination of both allowed the development of Arthrotest™, a diagnostic tool that allows one to determine the genetic predisposition of patients for suffering from severe, rapidly progressing knee osteoarthritis. It is an analysis that allows physicians to identify the worst prognosis patients and that, therefore, have an elevated risk of needing prosthetic surgery within a short amount of time.

"The clinical outcomes of primary knee osteoarthritis are highly variable. Some patients may live for years without suffering significant loss of functional capability or evident radiologic progression. Instead, others may end up disabled or needing prosthetic surgery in a few years. In this, genetics play a key role: rapid progression of knee osteoarthritis is hereditary in 60 to 70 percent of all cases”, declared Dr. Francisco J. Blanco, rheumatologist at the Institute for Biomedical Research from A Coruña (INBIC) and one of the leading authors of the study.

Methods and results of the study
In this study, 282 Caucasian patients participated who had been diagnosed with primary knee osteoarthritis. They were older than 40 at the moment of the diagnosis and had two radiographies available for assessment (one at the moment of diagnosis and another at the end of the monitoring period). Furthermore, the medical history of each patient was studied, analyzing variables such as gender, age at the time of diagnosis, location of osteoarthritis, and others.

Depending on results of the radiographic analysis, patients were classified into two prognostic groups: fast onset (i.e. worst prognosis) patients (those who have had to endure prosthetic surgery within an eight year period) and slow onset (or better prognostic) patients. Scientist analyzed 774 SNPs (Single Nucleotide Polymorphisms), registering clinical variable data as potential predicting markers.

Later, they developed a predictive mathematic model that was clinically validated in a second cohort of primary knee osteoarthritis patients.
The model thus obtained combined the information of a clinical variable (age at the time of diagnosis) and eight SNPs (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009). SNPs suppose 78 percent of the predictive capacity of the Arthrotest™ model, whereas the remaining 22 percent is explained by the clinical variant.

SNP rs2073508 within the TGFB1 gene (involved in the metabolism of arthrosis chondrocites) and SNP rs12009 within gene GRP78 (involved in the metabolism of glucose) are the SNPs with strongest contribution to the predictive ability of the model. Furthermore, this is the first time that a direct association between gene GCKR2 and osteoarthritis or its progression has been found. In that gene, associated by other studies with a higher risk of developing type 2 diabetes, we can find at least one of the eight SNPs of the Arthrotest™ model: rs780094.

Clinical Utility
The test, available to the public since June 2013, has an 82 percent precision level, a level that is considered excellent according to the international statistics standards. The analysis is performed only once in a lifetime and consists of extracting a saliva sample from the mouth of a patient diagnosed with knee osteoarthritis. DNA is extracted and analyzed in the laboratory and a report is presented to the physician detailing the risk level of that particular patient.

“Arthrotest™ helps physicians and patients to be more aware of this disease so that they can take action. The medical specialist may design a personalized treatment and the patient knows that his or her osteoarthritis will progress rapidly, thus making them take the treatment and the recommendations of his or her doctor more seriously”, declared Dr. Josep Vergés, Medical and scientific manager at Bioiberica and leading author of the study.

This test is the product of the Bioiberica Farma R&D department. Bioiberica is a Spanish biotech firm specializing in chondroprotector drugs against osteoarthritis and is one of the leading producers of heparin worldwide. In Spain there are more than 150 medical centers capable of performing this test.