Variants in a gene called DVWA may increase the risk of developing osteoarthritis (OA), according to a study published online in Nature Genetics.
“Our findings will help identify osteoarthritis pathogenesis mechanisms and aid development of improved diagnosis, treatment, and prevention methods,” conclude the researchers who were led by Shiro Ikegawa, MD, PhD, of the laboratory for Bone and Joint Diseases in Tokyo, Japan.
The researchers conducted a genome-wide association study of Japanese people with and without OA using ~100,000 single-nucleotide polymorphisms (SNPs). They identified DVWA, which is located on chromosome 3p24.3, and is expressed in cartilage. They replicated these findings in an additional Japanese group and a Chinese group.
Although the precise function of DVWA is not clear, the authors show that it binds to β-tubulin, and that this binding is weakened by the variants that are associated with elevated risk of OA. DVWA might modulate this activity of β-tubulin, and this could explain its association with OA.
Translating genetics into practice
The new research “adds another mechanism of action, which was not apparent before," said Tim Spector, MD, a professor of genetic epidemiology at King's College London in the UK.
“At this point in time, there are probably around six OA genes that have been replicated at least three times consistently in common disease,” he continued. “Our large European Union genetic consortium, Treat-OA, is working toward finding many more by pooling 20,000 samples from around the world.”
Asked by MSKreport.com whether this new research could yield new therapies, Dr. Spector responded, "Definitely. Novel mechanisms mean novel treatments—as well as improved prognostic indicators."
Reference
1. Miyamoto Y, Shi D, Nakajima M, et al. Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis, [published online ahead of print. July 11, 2008]. Nature Genetics. 2008; doi:10.1038ng.176 “Our findings will help identify osteoarthritis pathogenesis mechanisms and aid development of improved diagnosis, treatment, and prevention methods.” Shiro Ikegawa, MD, PhD.