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Scientists uncover new genetic variations linked to psoriasis
January 27, 2009Two international teams of researchers have made significant gains in understanding the genetic basis of psoriasis, a chronic skin condition that can be debilitating in some patients. Their research, involving thousands of patients, is reported in two studies published this week in the advance online Nature Genetics.
"Taken together, the studies help us get closer to realizing the promise of personalized medicine," says a senior author of both papers, Anne Bowcock, Ph.D., professor of genetics at Washington University School of Medicine in St. Louis. "Eventually, we hope to be able target treatments to psoriasis patients based on the genetic alterations that have contributed to their disease."
The researchers found a number of new genetic variants that affect an individual's risk of psoriasis. Their discoveries point to different biological pathways that underlie the disease and may eventually lead to targeted drugs and treatments that hit specific pathways, Bowcock says.
An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is usually characterized by red, scaly skin patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, which occurs when inflammation attacks the joints, causing pain and disability.
Both of the new studies looked for common variants in the genomes of psoriasis patients to uncover associations with the disease.
The first study, conducted in collaboration with the University of Michigan, the University of Utah and colleagues in Canada and Europe, focused on sites within the genome where a single unit of DNA is changed, called a single nucleotide polymorphism (SNP). The researchers scanned nearly 450,000 SNPs in each of the genomes of 1,409 psoriasis patients and compared the DNA variations to those in 1,436 healthy controls.
They initially discovered 21 suspect variants associated with psoriasis. Going one step further, the investigators tested the validity of these variants in another group of 5,048 psoriasis patients and 5,041 controls. This revealed a shorter list of confirmed variants - seven - all of which appear to increase the risk of the disease. Five of the variants cluster in two distinct pathways that involve the signaling molecules IL-23 and NF-kappaB.
A second study of 2,831 patients with psoriasis looked for links between the disease and copy number variations, in which a gene is produced in multiple copies. Bowcock and her colleagues in Barcelona, Spain and elsewhere found that the absence of two skin genes - LCE3B and LCE3C - increases the risk of psoriasis.
Both genes normally are activated after an injury to the skin. The researches suspect the absence of the genes could lead to an inappropriate immune response, which may cause the inflammation that is a hallmark of the disease.
"Until now, all of the genes linked to psoriasis have been involved in the immune system," Bowcock says. "But psoriasis is a disease of the immune system and the skin, and it makes sense that we would eventually find genes in the skin that are involved in the disease."
The new variants uncovered by the researchers each make only a small contribution to the overall genetic risk of the psoriasis. Patients usually have a number of different genetic variations that increase their risk of the disease.
Also, Bowcock noted that some of the newly discovered variants have been associated with other inflammatory diseases such as Crohn's disease and autoimmune diseases like rheumatoid arthritis and lupus. Additional studies will help to tease apart the ways in which these diseases are connected at the level of DNA. This information will also aid in the search for more targeted drugs that can zero in on particular genetic defects that cause the diseases.
Washington University School of Medicine
An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is usually characterized by red, scaly skin patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, which occurs when inflammation attacks the joints, causing pain and disability.
Both of the new studies looked for common variants in the genomes of psoriasis patients to uncover associations with the disease.
The first study, conducted in collaboration with the University of Michigan, the University of Utah and colleagues in Canada and Europe, focused on sites within the genome where a single unit of DNA is changed, called a single nucleotide polymorphism (SNP). The researchers scanned nearly 450,000 SNPs in each of the genomes of 1,409 psoriasis patients and compared the DNA variations to those in 1,436 healthy controls.
They initially discovered 21 suspect variants associated with psoriasis. Going one step further, the investigators tested the validity of these variants in another group of 5,048 psoriasis patients and 5,041 controls. This revealed a shorter list of confirmed variants - seven - all of which appear to increase the risk of the disease. Five of the variants cluster in two distinct pathways that involve the signaling molecules IL-23 and NF-kappaB.
A second study of 2,831 patients with psoriasis looked for links between the disease and copy number variations, in which a gene is produced in multiple copies. Bowcock and her colleagues in Barcelona, Spain and elsewhere found that the absence of two skin genes - LCE3B and LCE3C - increases the risk of psoriasis.
Both genes normally are activated after an injury to the skin. The researches suspect the absence of the genes could lead to an inappropriate immune response, which may cause the inflammation that is a hallmark of the disease.
"Until now, all of the genes linked to psoriasis have been involved in the immune system," Bowcock says. "But psoriasis is a disease of the immune system and the skin, and it makes sense that we would eventually find genes in the skin that are involved in the disease."
The new variants uncovered by the researchers each make only a small contribution to the overall genetic risk of the psoriasis. Patients usually have a number of different genetic variations that increase their risk of the disease.
Also, Bowcock noted that some of the newly discovered variants have been associated with other inflammatory diseases such as Crohn's disease and autoimmune diseases like rheumatoid arthritis and lupus. Additional studies will help to tease apart the ways in which these diseases are connected at the level of DNA. This information will also aid in the search for more targeted drugs that can zero in on particular genetic defects that cause the diseases.
Washington University School of Medicine
Psoriasis Current Events and Psoriasis News RSSCurry-cure? Spicing up the effectiveness of a potential disease-fighter
Scientists are reporting development of a nano-size capsule that boosts the body's uptake of curcumin, an ingredient in yellow curry now being evaluated in clinical trials for treatment of several diseases.
Skin-disease patients show brain immunity to faces of disgust
People with psoriasis - an often distressing dermatological condition that causes lesions and red scaly patches on the skin - are less likely to react to looks of disgust by others than people without the condition, new research has found.
Gene variation is 'major genetic determinant of psoriasis'
A specific genetic region that has been increasingly identified as the strongest genetic link to psoriasis has an even more significant role in the chronic skin disease than has been suspected, University of Utah medical researchers show in a new study.
Drug rescues memory lost to Alzheimer's disease
A drug similar to one used in clinical trials for treatment of rheumatoid arthritis and psoriasis has been found to rescue memory in mice exhibiting Alzheimer's symptoms.
Post-transplant combo can replace toxic immune-suppressing drugs in monkeys
Transplant patients rely on drugs to prevent graft rejection, but at the cost of serious side effects.
Psoriasis associated with cardiovascular disease and increased mortality
The skin disease psoriasis is associated with atherosclerosis (a buildup of plaque in the arteries) characterized by an increased prevalence of ischemic heart disease, cerebrovascular disease, peripheral artery disease and an increased risk of death.
Scientists discover new genetic immune disorder in children
Your immune system plays an important function in your health-it protects you against viruses, bacteria, and other toxins that can cause disease.
Study finds unexpected bacterial diversity on human skin
The health of our skin - one of the body's first lines of defense against illness and injury - depends upon the delicate balance between our own cells and the millions of bacteria and other one-celled microbes that live on its surface.
Vitamin D may halt lung function decline in asthma and COPD
Vitamin D may slow the progressive decline in the ability to breathe that can occur in people with asthma as a result of human airway smooth muscle (HASM) proliferation, according to researchers at the University of Pennsylvania.
Home UVB therapy for psoriasis as effective and safe as hospital treatment
For patients with psoriasis, treatment with ultraviolet B (UVB) at home is as effective and as safe as conventional hospital based phototherapy, concludes a study published on bmj.com today.
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