Scientists have linked nine genes to osteoarthritis, opening the door to new treatment possibilities.
Osteoarthritis is the most common form of arthritis, which cripples more than one in four adults worldwide, and, while medications can help to alleviate symptoms, there is no cure for the degenerative joint disease.
Five of the genes identified by the researchers from the University of Sheffield and the Wellcome Sanger Institute had distinctly different expressions in people who had arthritis and those who did not.
The discovery of these genes could offer new, more precise targets for arthritis treatments, the study suggests.
The nine newly-identified genetic causes for osteoarthritis could provide more precise treatment targets for the incurable disease that affects millions around the world
Arthritis of some form causes disability in more Americans than any other disease or illness.
The disease occurs when cartilage that provides cushion between bones wears down. Eventually, this wearing down can even reach the point that bones grind together, making movement excruciating.
Osteoarthritis is more commonly diagnosed among those over 65, but nearly two-thirds of people with arthritis are working-age, meaning that the days when they are in too much pain to work cost the economy as well, according to the Arthritis Foundation.
There is not much that can be done for these patients.
Doctors can treat the inflammation, pain and swelling caused by the action between their joints with drugs like Tylenol, ibuprofen or the antidepressant Cymbalta, which has been approved for treating arthritis pain as well.
Strengthening the muscles connecting the affected bones with physical therapy or light exercise, like yoga, may also help alleviate symptoms, but that won’t stop osteoarthritis from striking the knees of half of all adults.
Often, this persistent pain results in a knee replacement surgery (or hip, for those who develop the disease in these joints), which is costly and puts patients – who are often older and already at elevated risks for certain conditions – in danger of surgery-related heart attacks strokes and blood clots.
‘Treatments target the main symptom [of joint pain] and culminate in joint replacement, so it is very important that identify targets for development of new therapy,’ said Dr Eleftheria Zeggini, one of the new study’s lead authors.
Finding genetic targets for treatments could offer hope for an alternative treatment, but the 18 previously identified genetic associations for osteoarthritis were not expressed in ways that would make them viable targets.
After analyzing genetic data on nearly 328,000 people in the UK, Dr Zeggini and her team identified nine previously unknown locations in DNA whose expressions differed in people with and without osteoarthritis.
[This] is a major step for work identifying the potential targets
Dr Eleftheria Zeggini, study author
Then, to determine whether or not these genes might actually cause osteoarthritis, they tested two tissue samples from people who had had knee replacements: one of relatively healthy tissue, and one of the arthritic joint tissue.
‘By looking at the differences in genes in the primary tissue, we were able to pinpoint what those coded genes are most likely to be,’ and found five variations that coded for osteoarthritis, according to Dr Zeggini.
‘That is a major step for work identifying the potential targets,’ she added.
The researchers also looked at the connections between these genes and other conditions associated with osteoarthritis, including obesity and type 2 diabetes.
Obesity is the top preventable risk for osteoarthritis, and Dr Zeggini and her team were able to confirm that obesity is causal to arthritis because they found the same known genetic predispositions for obesity in people who also had osteoarthritis.
‘It’s not the first time that this has been shown, but we reaffirmed it and did this using the largest sample size to-date,’ said Dr Zeggini.
‘This is really relevant because osteoarthritis is the most prevalent musculoskeletal disease and the leading cause of disability and its prevalence is rising along with obesity, which is a modifiable risk factor,’ she added.
They also found that the genetic factors behind osteoarthritis of the knees and that affecting hips were 88 percent the same, a strong and previously uncertain commonality.
In order to turn their discovery into a treatment, Dr Zeggini says that experiments to alter genetic expression will next need to be done in cellular tissue models.
There are some ongoing osteoarthritis gene therapies in the US and the UK, and a handful of such treatments have been approved in other countries.
But now that we know the clear different expressions of these genes that lead to the disease, treatments down the line have far better targets to put in their sites.