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Osteoarthritis Risk May be in Your Genes

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Osteoarthritis Risk May be in Your Genes

Osteoarthritis Risk May be in Your Genes

August 19, 2004
By Stephanie Riesenman for Knee1
Achy joints? You can blame your parents. While it’s been established that obesity, previous injury, and infection are all causes of osteoarthritis, research is now beginning to show that one’s risk of developing osteoarthritis may be predetermined by their genetics. Osteoarthritis (OA) is a condition of the joints in which cartilage is progressively broken down until the bones, which were once separated by cartilage, begin to rub against each other. It may be the result of abnormal forces acting on a normal joint, or normal forces acting on a joint with abnormal tissues—such as cartilage or bone. Researchers have studied the genetic contribution to muscle strength, bone size, and cartilage volume. Each of these factors plays a role in the development of osteoarthritis, whereas a deficiency in any of these tissues elevates one’s risk for arthritis. A genetic abnormality may not only predispose someone to osteoarthritis, but it may also play a role in determining the age at which the disease appears, the joints it affects, the severity of osteoarthritis, and how quickly it progresses. Much of the research on the genetic risks of osteoarthritis has been conducted on families. There are three main strategies for studying the role of genetics in osteoarthritis. One approach is through twin studies in which researchers look for as many similarities between the siblings in regards to osteoarthritis and genes. The more similarities, the greater the likelihood their arthritis has a genetic root. Another approach is to identify patients with severe osteoarthritis and compare the patients’ incidence of OA to the incidence in other family members as well as to people with similar characteristics in the general population. In an English study of patients with osteoarthritis in multiple joints, the researchers found that osteoarthritis was more than twice as common in their relatives—mostly the older relatives and the females—than in the general population. Another approach is to study entire families by tracking the inheritance of OA from relative to relative. This type of study is underway in Iceland, where the geneology of the entire community has been recorded since the country was founded. Much of the inherited osteoarthritis identified by researchers in families around the world has been linked to specific mutations in genes—particularly those responsible for developing healthy cartilage. One example is a mutation in the DNA that makes up Type II collagen, a critical component of normal cartilage. Patients with the mutation have abnormal cartilage and eventually develop OA. In the April 2004 supplement to the Journal of Rheumatology, Dr. Roland Moskowitz, from Case Western University, explained that patients with abnormal cartilage due to genetic defects could spend their days in a sedentary occupation and never develop OA. But in other patients with the genetic defect, if the mechanical stresses on the cartilage are great enough, OA is likely to develop. This suggests that it is not necessarily genetics alone that causes a patient to develop arthritis, but is likely the interaction of their genes and the environment—such as exercise and injury—that triggers the condition. In the same issue of the Journal of Rheumatology, Dr. Michael Doherty, of Nottingham Medical School, reported that by looking at families with a rare form of osteoarthritis and identifying the gene defect, the percentage of siblings with osteoarthritis may be high, but it will have very little relevance to the forms of OA in the general population. In patients with more common OA, Dr. Doherty says they may be dealing with multiple abnormalities, each of which has a very small attributable risk of causing OA unless other environmental factors are present in those individuals. "It seems increasingly likely that we will find ourselves looking for a few—or even multiple—common polymorphisms, rather than for rare mutations, to explain the observed strong familial risk of OA," wrote Doherty. He goes on to say that there will likely be a long list of genes relating to a variety of processes that relate to the health of joints and the risk of developing osteoarthritis. Researchers hope that by learning about osteoarthritis genes and gene mutations, they will eventually be able to develop therapies to correct for or modify the effects of the mutations.

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