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Scientists unmask genetic markers associated with psoriasis
Date:1/25/2009

irst authors were Rajan Nair, Ph.D., assistant research professor of dermatology, and Jun Ding of the Biostatistics Department in the School of Public Health.

Within the past 18 months, researchers have increased the number of independent genetic "hotspots," or loci, confidently associated with psoriasis from oneHLA-Cw6, previously identified by Elder, et al., in 2006to 10. Four of these have been identified for the first time by this study, and two more have since been confirmed by these researchers.

Research details

The team looked for single nucleotide polymorphisms (SNPs), or DNA changes, at 438,670 sites in 1,359 psoriasis cases and 1,400 healthy controls. Initial scans signaled differences in at least three previously identified DNA sites, with HLA-Cw6 producing the strongest genetic signal. They then expanded the study to look at 18 of the most interesting loci in an additional 5,048 cases and 5,051 controls.

In all, seven of the 18 loci showed consistently strong association with psoriasis. As a result, four proteins produced from the altered DNA code now can be targeted for further study.

This study is the first to identify changes in the IL23A gene in psoriasis patients. Notably, two of the previously identified psoriasis genes (IL12B and IL23R) encode proteins that bind to IL23A protein. Variations in the structure any of these three genes may predispose people to chronic immune responses that ultimately result in psoriasis.

The team also found that genetic signals for proteins activated by TNF-, a key signaling molecule involved in inflammation, are distinct from the patterns in healthy controls. Two genes activated by TNF-TNFAIP3 and TNIP1show strong association with psoriasis. Together, these genes limit immune responses. Genetic alterations in this "brake" may allow the immune system to work overtime within the skin. Variants of TNFAIP3 also have been associated with rheum
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Contact: Katie Vloet
kgazella@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

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