Identification of a previously unknown gene linked to knee arthritis provides new therapeutic target
Molecular geneticists in Japan and China have identified a previously unknown gene associated with susceptibility to osteoarthritis (OA), a common disease affecting the functioning of knee and hip joints through abnormal wearing of the cushioning cartilage. The researchers have named the newly identified gene DVWA (double von Willebrand factor A) and suggest that it codes for a protein involved in the formation of cartilage. The discovery could lead to genetic diagnosis of some forms of knee OA, and possible development of a therapeutic drug.
More than one adult in 10 over the age of 50 suffers from OA, a painful condition that restricts movement. Genetic susceptibility to OA is largely a mystery, although a few genes are already known to be associated with it.
In a recent paper in Nature Genetics (1), researchers from RIKEN’s Center for Genomic Medicine in Tokyo and Yokohama together with colleagues from several medical schools describe how they screened about 100,000 point mutations or single nucleotide polymorphisms (SNPs) from the Japanese SNP database to find the previously unknown gene.
Initially the researchers screened the genomes of 94 Japanese sufferers of knee OA and about 650 controls against the whole set of SNPs. About 2% of these SNPs were significantly correlated with OA. These were then tested against the genomes of an independent group of about 900 Japanese OA patients and 1,100 controls, and a third group of more than 400 Han Chinese OA sufferers and a similar number of controls. Several of the SNPs significantly associated with knee OA occurred in the DVWA gene. This association was independent of age, body mass index and sex.
The researchers determined in the laboratory that the DVWA protein binds to a protein building block of microtubules, â-tubulin. Microtubules are structural components of cells, which are associated with internal transport and have also been reported to play a role in the differentiation of cartilage-forming cells. Two of the SNPs of DVWA significantly weaken its protein product’s capacity to bind to â-tubulin.
“We are now planning to check the replication of our results in other ethnic groups to examine whether DVWA is a ‘global’ gene or not,” says Shiro Ikegawa, who led the research project. “And we also intend to clarify our proposed molecular mechanism as to how SNPs of the gene make people susceptible to OA.”
1. Miyamoto, Y., Shi, D., Nakajima, M., Ozaki, K., Sudo, A., Kotani, A., Uchida, A., Tanaka, T., Fukui, N., Tsunoda, T., Takahashi, A., Nakamura, Y., Jiang, Q. & Ikegawa, S. Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. Nature Genetics 40, 994–998 (2008).
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences