The debilitating knee, hip, wrist or back pain associated with osteoarthritis (OA) is commonplace within diverse populations around the world and represents a broadly recognized hallmark of old age, yet remarkably little is known about the origins of this disease.
Most evidence suggests that OA arises from a mix of genetic and environmental factors, but researchers of this disease, including Shiro Ikegawa of the RIKEN Center for Genomic Medicine in Tokyo, have found it a considerable challenge to uncover risk factor genes. “It is our long-standing dream to know the ‘real cause’ of this disease,” says Ikegawa, “but it has proven very difficult.”
Advances in techniques for genomic analysis have now enabled his group and a team of collaborators from across Japan and Europe to achieve an important breakthrough on this front1. They screened over 4,000 Japanese individuals—906 with OA of the knee, and 3,396 unaffected control subjects—in an effort to identify genome sequence variations that exhibit a statistically significant association with this condition. Of fifteen candidates identified in this initial search, two of these ‘single nucleotide polymorphisms’ (SNPs) warranted further close scrutiny.
Unexpectedly, the researchers found that both of these SNPs are located within a region of chromosome 6 containing numerous genes involved in the immune response: the rs7775228 variation occurs near genes that help instruct immune cells to ignore host proteins, while rs10947262 falls within a gene that controls T cell activation. “OA has long been thought of as having only limited association with immunological abnormalities,” explains Ikegawa, “but it turns out this is not the case.” These results are also in keeping with a handful of recent studies that have hinted at an inflammatory component of OA pathology.
Intriguingly, the team noted that simultaneous variations at both sites were more significantly associated with OA among Japanese subjects than either of the two SNPs individually. On the other hand, the disease association of this particular combination of SNPs—also known as a ‘haplotype’—was less notable among a European sample group.
Many more risk factors likely remain to be discovered—including some that may be specific to OA affecting individual body parts—and Ikegawa and colleagues are now moving on to larger scale association studies to characterize additional genes. He adds that such efforts are only a beginning. “Association is just statistics,” he says. “After finding associations, we need to prove functionality of the genes and SNPs to achieve our final goal of treating OA.”
The corresponding author for this highlight is based at the Laboratory for Bone and Joint Disease, RIKEN Center for Genomic Medicine
1. Nakajima, M., Takahashi, A., Kou, I., Rodriguez-Fontenla, C., Gomez-Reino, J.J., Furuichi, T., Dai, J., Sudo, A., Uchida, A., Fukui, N. et al. New sequence variants in HLA Class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study. PLoS ONE 5, e9723 (2010)
Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System
Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
22.08.2017 | Health and Medicine
22.08.2017 | Materials Sciences
22.08.2017 | Life Sciences