Variations in a single gene simultaneously increase the risk of two autoimmune conditions
Japanese researchers have identified two single nucleotide polymorphisms (SNPs), each of which significantly increases susceptibility to the autoimmune diseases rheumatoid arthritis (RA) and systemic lupus erythmatosus (SLE). They occur in a gene for a protein that regulates immune system cells. While the SNPs have so far only been detected in East Asians, understanding their role in promoting the onset of both autoimmune diseases could lead to better treatments for all, the researchers say.
RA is a painful condition where the body’s immune system attacks and degrades joints. The disease affects up to one person in a hundred, and both genetic and environmental factors can increase susceptibility to it. Other researchers have uncovered several genes with variants that increase the risk of RA. Some, presumably for compounds involved in the autoimmune process at a generic level, simultaneously increase the risk of other autoimmune conditions, such as SLE.
The current study, recently published in Nature Genetics (1), was led by researchers from RIKEN’s Center for Genomic Medicine in Yokohama. It focuses on a region of the long arm of human chromosome 1 which contains genes of the signaling lymphocyte activation molecule (SLAM) family. Proteins of the SLAM family are involved in regulating cells of the immune system, so there is a potential link with autoimmune conditions. The chromosome region had already been linked with increased risk of RA and SLE in previous studies.
In two independent Japanese populations—one of 830 arthritis sufferers and 658 controls, the other of 1,112 arthritis sufferers and 940 controls—the researchers identified five SNPs closely associated with RA in the SLAM family gene, CD244. The researchers showed that these SNPs also increase susceptibility to SLE.
All the SNPs occurred in the gene’s introns—segments of the DNA sequence that are chopped out before the final protein is synthesized. It has recently been suggested that introns may well play a role in regulating gene activity. So the researchers assayed the SNPs for their impact on the rate of transcription of CD244, and determined that two of five led to significant increases in gene activity.
As CD244 is known to encode a protein which activates or inhibits the natural killer cells of the immune system, the researchers say they are not surprised that its SNPs are associated with susceptibility to autoimmune diseases. “But we don’t yet know the precise molecular mechanisms involved,” says project leader, Kazuhiko Yamamoto.
1. Suzuki, A., Yamada, R., Kochi, Y., Sawada, T., Okada, Y., Matsuda, K., Kamatani, Y., Mori, M., Shimane, K., Hirabayashi, Y., et al. Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population. Nature Genetics 40, 1224–1229 (2008).
The corresponding author for this highlight is based at the RIKEN Laboratory for Autoimmune Diseases
Further reports about: > Arthritis > CD244 > Chromosome > Genetics > SLAM > SLE > SNP > autoimmune > autoimmune conditions > autoimmune diseases > immune system > molecular mechanism > rheumatoid arthritis > signaling lymphocyte activation molecule > single nucleotide polymorphisms > systemic lupus erythmatosus
Antibiotic resistances spread faster than so far thought
18.02.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
The Lypla1 Gene Impacts Obesity in a Sex-Specific Manner
18.02.2019 | Deutsches Zentrum für Diabetesforschung
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...
Physicists from the University of Basel have developed a new method to examine the elasticity and binding properties of DNA molecules on a surface at extremely low temperatures. With a combination of cryo-force spectroscopy and computer simulations, they were able to show that DNA molecules behave like a chain of small coil springs. The researchers reported their findings in Nature Communications.
DNA is not only a popular research topic because it contains the blueprint for life – it can also be used to produce tiny components for technical applications.
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
18.02.2019 | Interdisciplinary Research
18.02.2019 | Process Engineering
18.02.2019 | Studies and Analyses