Advancing age, injury and excess weight usually top the list when people think about the causes of osteoarthritis, or OA. But scientists are increasingly discovering genetic links to this common form of arthritis that strikes 1 in 5 adult Americans. In a new study, published in 2011 in the American Journal of Human Genetics, researchers in the United Kingdom say they’ve discovered a third gene that could be associated with the painful and debilitating disease.
“This gene is on a different chromosome [than] the other two established OA loci,” Eleftheria Zeggini, PhD, the study’s senior author, writes in an email. “We find that it increases the risk of developing osteoarthritis.” Zeggini heads the applied statistical genetics group at the Wellcome Trust Sanger Institute, a genome research facility near Cambridge.
The new marker was found on a gene known as MCF2L, on chromosome 13, which helps regulate nerve growth factor, or NGF, a protein involved in growing and maintaining nervous system cells.
A previous study, published in the New England Journal of Medicine in 2010, showed treatment with anti-NGF reduced OA-related knee pain.
“This suggests that MCF2L is involved in the development of osteoarthritis and provides a new focus for future research,” Zeggini writes.
Researchers compared the genomes, or genetic material, of more than 3,000 OA patients to those from nearly 5,000 people in the general population, looking at 600,000 variants. They then compared that information to data from the existing 1000 Genomes Project, searching through another 7 million gene variations. That’s when they found the disease-associated variant in the MCF2L gene.
“The frequency of a variant in the gene is significantly higher in OA patients compared to controls,” Zeggini explains. “We cannot be certain that this particular gene is causal until functional studies are carried out, but this new association serves as an important clue for instigating these studies.”
Zeggini says that the heritability of OA has been estimated to be between 40 and 60 percent. Two other gene variants have been linked to OA: one on chromosome 20 and another on chromosome 7.
Terry Moore, MD, director of the rheumatology division at Saint Louis University, says it’s important to note that there is some genetic predisposition to OA.
“Normally we consider it a traumatic wear-and-tear process, but we do know there is some inherited process,” Dr. Moore says. “It’s not all trauma, increased weight and age.”
But Dr. Moore says that, although the findings are interesting, the clinical significance of this study is minimal right now, in part because all of the OA patients and controls in this study were of European descent. “Is it a general marker or just for one genetic group?” he asks.
Genetic screening is also very expensive, Dr. Moore says, making it unrealistic to do for the majority of patients. And ultimately, the results might hurt patients more than help them. “That’s the question about genetic testing: If the insurance company discovers it, could it affect coverage?” he asks.
Researchers, however, are optimistic, saying they’re hopeful this discovery will lead to new areas of research and potentially new treatments.