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Genetic mystery of Behcet's disease unfolds along the ancient Silk Road
Date:1/6/2013

n inflammatory conditions such as psoriasis, inflammatory bowel disease and a form of spinal arthritis called ankylosing spondylitis.

Among the newly identified regions, researchers found:

  • An important association between Behcet's disease and a gene called ERAP1. ERAP1 codes for a molecule that processes microbial proteins in white blood cells. Variants of this protein can lead to more or less efficient processing of microbial proteins before they are loaded onto HLA molecules for presentation to the immune system. The variants of ERAP1 identified in this study increase the risk of Behcet's disease, but only in those individuals with one specific HLA type, HLA-B51, which has previously been associated with Behcet's disease. Dr. Kastner speculates that the ERAP1 variant associated with Behcet's disease processes microbial proteins in such a way that they can be loaded onto the HLA-B51 molecule to trigger an abnormal immune response. The very same variant of ERAP1 that is associated with Behcet's disease is protective for ankylosing spondylitis and psoriasis, but only in people with the HLA types associated with those diseases.

  • A significant association of Behcet's disease with variants near the CCR1 gene. Proteins coded by this gene help infection-fighting blood cells migrate to sites of invading microorganisms. When this function is defective, the microorganisms can trigger a persistent inflammatory response.

  • An association of the disease with variants in the KLRC4 gene. The function of the receptor protein coded by this gene is not well understood, but the researchers suggest that it may be important to investigate further because it is located within the genomic region with the strongest evidence for linkage to a disease gene in a study of Turkish family health histories in which members sometimes have a rare familial form of Behcet's disease.

  • An association with the STAT4 gene, in which diffe
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Contact: Raymond MacDougall
macdougallr@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
Source:Eurekalert

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