Researchers uncover new genetic links to psoriasis

April 03, 2008

In a comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of this troublesome skin condition. They also found that variations in one genetic region link psoriasis and psoriatic arthritis to other autoimmune disorders. These results appear April 4 in the open-access journal PLoS Genetics.

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 characterized by red, scaly patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, a condition that is often excruciatingly painful and debilitating.

"Common diseases like psoriasis are incredibly complex at the genetic level," says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. "Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis."

In their study, the researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that comprise DNA are thought to be identical from one person to the next, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person's predisposition to disease or good health.

Using an approach known as whole genome association, the investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in 519 healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients - 577 with psoriasis and 576 with psoriatic arthritis - and more than 1,200 healthy controls.

Bowcock and her team found seven novel DNA variations linked to psoriasis. Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland), and celiac disease (caused by the inability to digest gluten).

The variations identified by this research team point to different biological pathways that underlie psoriasis and may eventually lead to new targeted drugs and treatments that hit specific pathways, Bowcock says.

Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis. Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.
-end-
The research was supported by grants from the National Institutes of Health.

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plosgenetics.org/doi/pgen.1000041 (link will go live on Friday, April 4)

CITATION: Liu Y, Helms C, Liao W, Zaba LC, Duan S, et al. (2008) A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci. PLoS Genet 4(3): e1000041. doi:10.1371/journal.pgen.1000041

CONTACT:

Caroline Arbanas
(314) 286-0109
arbanasc@wustl.edu

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