First gene linked to common form of psoriasis identified
Scientists led by Washington University School of Medicine in St. Louis have identified the first gene directly linked to the most common form of psoriasis. Rare mutations in the CARD14 gene, when activated by an environmental trigger, can lead to plaque psoriasis, which accounts for 80 percent of all cases of the condition. Credit: National Psoriasis Foundation
Scientists led by Washington University School of Medicine in St. Louis have identified the first gene directly linked to the most common form of psoriasis, a chronic skin condition.
The research shows that rare mutations in the CARD14 gene, when activated by an environmental trigger, can lead to plaque psoriasis. This type of psoriasis accounts for 80 percent of all cases and is characterized by dry, raised, red patches covered with silvery scales that can be itchy and painful.
The new findings also indicate that mutations in CARD14 can be involved in the pustular form of psoriasis and in a debilitating arthritis linked to the psoriasis. The discovery may lead to more effective, targeted therapies for plaque psoriasis and other forms of the disease.
The research is published May 4 in two separate papers in The American Journal of Human Genetics.
"We have searched for almost two decades to find a single gene linked to plaque psoriasis," says the senior author of both papers, Anne Bowcock, PhD, professor of genetics. "Individually, the rare mutations we have found likely confer a high risk for the disease, and we think they will be important in the search to find new, more effective treatments."
Although psoriasis has long been thought to be caused by an overactive immune system, the genetic pathway uncovered by the scientists points to defects in the skin as the main culprit of the condition and to immune cells as secondary players.
Now, the researchers want to find out how common the altered pathway is in the different types of psoriasis and in patients with psoriatic arthritis. Their work suggests that in at least some patients with different forms of psoriasis, this pathway is the same.
An estimated 7.5 million Americans have psoriasis, and about 30 percent of them develop psoriatic arthritis. Like other common diseases, psoriasis runs in families and has been thought to have a genetic component, but it's been difficult to pin down the genes involved. That's because common variations in genes likely contribute very little to the overall genetic risk of the disease, and mutations that substantially increase a person's risk are so rare they have been impossible to find.
With early support from the National Psoriasis Foundation, Bowcock initiated the research with co-author Alan Menter, MD, of the Psoriasis Research Institute at the Baylor College of Medicine.
Using the latest DNA technology to sequence all of a patient's genes, Bowcock and her colleagues uncovered a rare CARD14 mutation in a large family of northern European descent in which plaque psoriasis was prevalent. They also found the mutation in the one-third of family members who had developed psoriatic arthritis, suggesting that the same rare mutation can play a role in both conditions.
The scientists also identified another rare CARD14 mutation in an extended family from Taiwan that had a large number of plaque psoriasis cases.
But mutations in the gene do not only occur in families with a genetic predisposition.
The researchers, including the papers' first author Catherine Jordan, an MD/PhD student at Washington University, also found a CARD14 mutation in a 3-year-old girl with a severe case of pustular psoriasis, a rare form of psoriasis. Neither of the girls' parents had mutations in CARD14, indicating that the rare mutation was not inherited but had occurred spontaneously.
Psoriasis typically develops after an environmental trigger, which can include an infection, such as strep throat, or injury to the skin, including a cut or bug bite. Certain medications, smoking and heavy alcohol consumption also are triggers.
The young girl, from Haiti, developed psoriasis in infancy, like some members of the family with origins in northern Europe.
"This is significant because it tells us that CARD14 mutations alone are enough to lead to psoriasis, possibly after an early trigger such as an infection," Bowcock explains. "You don't need anything else. This really highlights the importance of finding rare mutations for common diseases like psoriasis."
The researchers also found 15 other rare mutations in CARD14. In a finding that is statistically significant, the mutations were more common in more than 6,000 patients with psoriasis compared to 4,000 healthy controls.
The scientists showed that in specialized skin cells called keratinocytes, mutations in CARD14 increase the activity of NF-kappaB, a protein that turns on genes. This protein increases the production of certain signaling molecules that attract inflammatory cells to the skin, unleashing a vicious cycle of inflammation that is so notable in psoriasis.
Psoriasis affects the life cycle of skin cells, causing them to mature rapidly in just a few days and accumulate to form thick, scaly patches. Interestingly, in psoriasis patients with CARD14 mutations, the researchers found the gene's activity was increased in the upper layers of the skin, which may explain the flakiness that characterizes the condition.
"Now, we have a much clearer picture of what is happening in psoriasis," Bowcock says. "And with all kinds of new therapeutic targets that lie within the CARD14 pathway, the field is wide open."
More information: The American Journal of Human Genetics. May 4, 2012. www.cell.com/AJHG/
Provided by Washington University School of Medicine
- Researchers uncover new genetic links to psoriasis Apr 04, 2008 | not rated yet | 0
- Relief from red, itchy skin: Unraveling the secrets of vitamin D May 12, 2011 | not rated yet | 0
- Coffee, caffeine not linked to psoriasis in U.S. women Mar 21, 2012 | not rated yet | 0
- Researchers receive largest single collection of psoriasis DNA samples Sep 01, 2010 | not rated yet | 0
- Smoking is an independent risk factor for psoriasis Mar 07, 2012 | 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
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics 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 ...
13 hours ago | 4.2 / 5 (5) | 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. ...
11 hours ago | 4.9 / 5 (9) | 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.
7 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 ...
8 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.
13 hours ago | 4.5 / 5 (6) | 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.
9 hours ago | 5 / 5 (1) | 0 |