Posted on 07/26/2006 3:54:33 AM PDT by Pharmboy
U-M scientists find new genes linked to rheumatoid arthritis that are expressed differently in genetically identical twins Ann Arbor, Mich. -- They sleep together, eat together, and most people find it impossible to tell them apart. Identical twins who grow up together share just about everything, including their genes. But sometimes only one twin will have health problems when genetics predicts both of them should.
Scientists at the University of Michigan Medical School are just beginning to understand how two people who are so similar biologically can be so different when it comes to the development of diseases like rheumatoid arthritis.
U-M researchers have discovered three genes that are over-expressed in rheumatoid arthritis, or RA, that were not known to be associated with the disease before. They also found that non-genetic factors influenced the expression of these genes and that the expression patterns varied between identical twins where only one twin had RA. Results of the U-M study were published in the July issue of Arthritis and Rheumatism.
RA is a chronic inflammatory disease that damages joints. RA causes pain, loss of movement, and bone deformities. It affects 2.1 million Americans. There are many genetic factors that put people at a high-risk for developing RA, yet only 15 percent of identical twins will both develop it.
Scientists compared gene expression patterns of 11 pairs of monozygotic twins, who shared the same egg and were genetically identical, but only one of them had RA. They found three new genes that were significantly over-expressed in the twin with RA compared to the one without the disease. This is the first report for RA that examines gene expression patterns in monozygotic twins.
"This is the crux of the issue we are trying to address in RA -- how two patients can have the same genes but different disease outcomes. Identical twins represent the best experimental system to address this question," says Joseph Holoshitz, M.D., an associate professor of internal medicine at U-M Medical School and co-author of the study.
The advantage of studying twins is that they start out with the exact same genetic information. Therefore, differences in gene expression are attributable to different environmental factors rather than genetics. Such factors could cause a random genetic mutation or affects how DNA is packaged.
"There's a lot of variability in the severity of the disease, symptoms, and the response a patient will have to treatment. Differences in the expression of genes caused by environmental factors that modify DNA have a lot to do with this variability," says Holoshitz.
The most significantly over-expressed of the three genes codes for a protein called laeverin. This is an enzyme that destroys certain types of proteins. Scientists hypothesize that laeverin promotes the tissue damage of the joint found in RA by degrading cartilage and bone.
Another previously unidentified gene codes for a protein called 11â-HSD2 that helps deactivate the hormone cortisol. This hormone is involved in the response to stress and also has anti-inflammatory effects. The discovery that 11â-HSD2 is over-expressed in patients may explain a common characteristic of RA patients.
"It has been known for a long time that there is a deficiency of cortisol in RA patients," says Holoshitz.
The third gene U-M scientists discovered codes for Cyr61, which plays a role in angiogenesis, a process that recruits new blood vessels to an area.
In the early stages of RA, the tissue in the joint begins to grow and divide similarly to a benign tumor. The growing mass, which secretes proteins that degrade tissue, uses angiogenesis to recruit new blood vessels to supply it with nutrients. The angiogenic factor Cyr61 could be involved with this process.
"This paper describes only a glimpse of what this approach might reveal. There are many other categories of genes where expression varies between twins. We are just beginning to understand how RA is able to affect people in different ways. The newly discovered genes provide important insights into the nature of the disease and facilitate the design of novel treatment strategies for RA," says Holoshitz.
Contact: Rossitza Iordanova rossitza@med.umich.edu 734-764-2220
### The study was supported by the National Institutes of Health, the Arthritis Foundation, and the Office of Research and Development, Department of Veterans Affairs.
The lead authors were Christian S. Haas, M.D., a research fellow in the department of internal medicine at U-M Medical School; and Chad J. Creighton, a research assistant in the department of pathology at U-M Medical School. Additional contributing authors from the U-M Medical School were Xiujun Pi, M.D., Ph.D., a research fellow in the department of rheumatology; Ira Maine, Ph.D., research associate in the department of pathology; Alisa E. Koch,M.D., professor of rheumatology and internal medicine, Song Ling, Ph.D., a research investigator in the department of internal medicine; Arul M Chinnaiyan, M.D., Ph.D., an associate professor of pathology and urology. G. Kenneth Haines, III, M.D. from Northwestern University Feinberg Medical School also contributed.
Reference: Arthritis and Rheumatism, Vol. 54, No. 7, July 2006, pp 2047-2060.
For more information on rheumatoid arthritis visit:
Adult Health Advisor: Rheumatoid Arthritis: http://www.med.umich.edu/1libr/aha/um_rheuarth_sha.htm
Geez...doesn't that U-M internist have a most unfotunate name? I do not think anyone would blame him for changing it...
Incredible name for an internist at U-M Medical School ping list combined with non-identical identical twin ping list...
Laz--you and pissant are on for the former ping list.
>>This could have implications far beyond rheumatoid arthritis<<
Like the "Gay Gene"?
Do you mean him? I was once fooled by a prankster-I called the funeral home and asked for Myra Maines. It took me a week to figure out the punch line.
We once that that the genes were the be all and end all of life. We thought that cracking the human genome would answer all of our questions, but we were wrong. Life is far more complex than a set of instructions, its how they are interpreted that counts, and that interpretation depends on alot of external factors.
auto-immunity, whether or not exposed to infection, not mentioned as possible etiologic factors.
"Dr. Holoshitz will see you now..."
That is certainly understood...I believe that the authors would have assumed its readers would be aware of that. Their main focus here, however, was the the three genes they isolated as possibly being the keys here.
Probably why he decided against being a proctologist
Now THAT'S funny...
Talk about missing the elephant in the room...
Thanks for the ping!
I think he is referring to Joseph Holoshitz, M.D., mentioned in the forth or fifth paragraph. That would be a tough name to grow up with
I believe the internist is in the process of changing it to Solidshitz.
Ping
IIRC, he joined the army and became General Sheisskopf.
This kind of thing where a gene is expressed in one individual and not in another "genetically identical" is not surprising to me.
The process of lysogeny in bacteria is well known. Two identical bacteria, infected with the same Lambda phage may either go into a lysogenic state or a lytic state. The key is a "fight" with a repressor. If the balance swings one way the bacterium survives, harboring the lysogenic phage. If the balance swings the other, new virus particles are produced and the bacterium is killed. Why couldn't the same general process happen in identical twins?
I would like to point out that the lead author is a Christian.
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