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Gene Discovery Links Osteoarthritis to Nerve Growth Factor

A collaborative genetic project has unearthed a third genetic link to osteoarthritis. The gene regulates nerve growth factor, providing logic behind a treatment that has already been tested and found worthy.

Sifting through the massive data in the 1000 Genomes Project, an international effort to amass and scrutinize a very large number of individual human genomes, researchers have unearthed a third genetic linkage to osteoarthritis (OA). The association involves a variant of gene called MCF2L, which regulates the function of neurotrophin-3, a member of the nerve growth factor (NGF) family of signaling molecules.

The study involved investigating the genotypes of 19,041 people with arthritis and 25,504 people without the condition in Iceland, Estonia, the Netherlands, and the UK. The report of the newfound genetic marker for osteoarthritis appears in the American Journal of Human Genetics.

The gene variant in question is associated more closely with knee osteoarthritis than with OA of the hip. Last October, US researchers reported in the New England Journal of Medicine that a monoclonal antibody directed against NGF reduced pain and improved function among patients with OA of the knee.

The finding is also a validation of the genetic methods, which involve looking for low-frequency changes in small genetic sequences within common variants of a gene--an effort possible only by studying very large numbers of individual genomes. Further studies using the same techniques, the authors say, "hold the promise of providing insights into the etiology of this common degenerative joint disease."