Team pinpoints amino acid variation in immune response gene linked with ulcerative colitis
The association between the inflammatory bowel disease ulcerative colitis and a gene that makes certain cell surface proteins has been pinpointed to a variant amino acid in a crucial binding site that profoundly influences immune response to antigens, including gut bacteria, reports a team of researchers at the University of Pittsburgh, Cleveland Clinic, Carnegie Mellon University and Harvard Medical School. They published the findings today in the online version of Genes & Immunity.
Variations in genes that regulate immune responses in a region of chromosome 6 have long been linked with susceptibility for many infectious and chronic inflammatory conditions, including ulcerative colitis, said Richard H. Duerr, M.D., professor of medicine, Pitt School of Medicine, co-director and scientific director, UPMC Inflammatory Bowel Disease Center, and the corresponding author of the study. Ulcerative colitis is characterized by recurrent inflammation of the large intestine that results in diarrhea mixed with blood and abdominal pain.
"We tested more than 10,000 points, called single nucleotide polymorphisms, or SNPs, in the gene sequence in this chromosomal region, and we also tested amino acid variations in human leukocyte antigen (HLA) proteins that were deduced from the SNPs to identify those most important for ulcerative colitis," Dr. Duerr said. "Refining the gene association signals in this region enabled us to better understand the underlying mechanisms of the disease."
Using sophisticated association techniques, the authors confirmed that an HLA gene called DRB1, which codes for a protein that is involved in the immune response and routinely tested in tissue matching for organ transplantation, was uniquely related to ulcerative colitis. Variation, or polymorphism, in that gene altered which amino acid was selected for the 11th position in the DRB1 protein a key location because it is in a pocket of the so-called binding cleft where other proteins, such as antigens or markers of foreign cells, attach.
"This particular position probably plays a significant role in determining the human immune response to extracellular antigens," Dr. Duerr said. "It ties into theories that ulcerative colitis might result from an abnormal immune response to gastrointestinal bacterial antigens or might be an autoimmune disorder caused by an abnormal immune response to a self-antigen."
The researchers also looked for a similar relationship between that amino acid position and Crohn's disease, another chronic inflammatory bowel condition, but did not find a strong association. Still, variants in immune response genes on chromosome 6 likely contribute not only to ulcerative colitis and Crohn's disease, but also to other immune-mediated diseases such as rheumatoid arthritis and multiple sclerosis, added Jean-Paul Achkar, M.D., Department of Gastroenterology & Hepatology, Cleveland Clinic Digestive Disease Institute, an alum of the gastroenterology and hepatology training program at UPMC, and first author of the study.
- New genetic markers for ulcerative colitis identified Jan 04, 2009 | not rated yet | 0
- Identification of genetic markers for ulcerative colitis could lead to treatment Jan 08, 2009 | not rated yet | 0
- Research team identifies genes linked to ulcerative colitis Mar 17, 2010 | not rated yet | 0
- Which treatment is effective in maintaining remission in ulcerative colitis: Probiotic or placebo? Apr 19, 2010 | not rated yet | 0
- Gene associated with ulcerative colitis uncovered by researchers Aug 03, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Is energy convertible to matter?
2 hours ago Can we convert energy to matter?
Rotating electron as a dipole is this right?
4 hours ago An electron as shown by the Stern Gerlach experiment behaves like a dipole (albeit only in one of two states). I have been trying to figure out how...
Dipole term in multipole expansion
8 hours ago Hi. I'm having some difficult in understanding something about the dipole term in a multipole expansion. Griffiths writes the expansion as a sum of...
Bubbles in a Pre-Boiling/Boiling pot of water
9 hours ago How is it that bubbles form on the bottom of a surface of a pot of boiling water? I think that there is probably an elementary answer to this...
Assumptions of Griffith's fracture theory
20 hours ago Any experts on Griffith's fracture theory? I am studying the subject and I am having hard time finding out if the theory is valid for all possible...
Current leading voltage or vice versa concept
21 hours ago Hello, I was wondering if there is a conceptual explanation for when current leads voltage or vice versa for capacitors or inductors with AC...
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (21) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology May 20, 2013 | 5 / 5 (5) | 0 |
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
11 hours ago | 4 / 5 (4) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
9 hours ago | 4.9 / 5 (8) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
4 hours ago | 3 / 5 (2) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
5 hours ago | 5 / 5 (3) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
11 hours ago | 4.8 / 5 (4) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
6 hours ago | not rated yet | 0 |