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Researchers identify 4 genetic hotspots associated with psoriasis
Date:1/26/2009

important to the pathogenesis of psoriasis, according to Krueger.

The researchers took advantage of a new technology called genomewide association studies (GWAS). At the heart of this is selecting from the more than10 million polymorphisms (mutations) in the human genome a group of polymorphisms that are predicted to be informative of association with disease, in this case psoriasis. The platform used in this experiment contained 438,670 polymorphisms. To assess for psoriasis-associated polymorphisms each of the 1,359 subjects with psoriasis and a control group of 1,400 people without the disease had their DNA probed for each of the 438,670 polymorphisms. After identifying 18 DNA sites with the highest associations with psoriasis, the researchers expanded the study to include 5,048 people with psoriasis and 5,051 without the disease. From that, the researchers identified seven potential genetic hotspots for psoriasis.

Three of those sitesIL-12B, IL-23R and IL-13 were first identified in earlier studies by Krueger and other University of Utah and Celera Group researchers. A third gene, HLA-C, has the strongest association with psoriasis and has been found numerous times by many investigators. Most recently, the Elder group showed this association appears to be linked to an allele of HLA-C called *0602, and the latest study confirms this, once again. Three new polymorphisms reported in the Nature Genetics studyIL-23A, TNFAIP3, and TNI1had not been linked to the skin and joint disorder, and in addition there has been confirmation of IL-13 and a closely linked partner IL-4.

The researchers concluded that IL-12B and IL-23-R encode proteins that bind to IL-23A and that mutations in any of those genes may predispose people to immune responses that lead to psoriasis. The study also showed that genetic signals from two regulatory elements, TNFAIP3 and TNI1, of TNF-alpha, may be faulty regulating the TNF-alpha induced inflammation of p
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Contact: Phil Sahm
phil.sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

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