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Dec 24, 2009

Investigators Find Genetic Basis to Clustering Effect Seen in Autoimmune Diseases

  • Scientists at Stanford University School of Medicine have uncovered a genetic basis for why people with a particular autoimmune disease are often predisposed to another autoimmune disease. Their research also demonstrated that two such clusters tend to be mutually exclusive.

    The study is published online December 24 in PLoS Genetics. It is titled “Autoimmune disease classification by inverse association with SNP alleles”.

    Pairs of autoimmune diseases have been linked in clinical practice. For example, people with type 1 diabetes are at a higher risk for autoimmune thyroid disease. However, no one has ever known why these clusters exist, the Stanford team points out.

    Atul Butte, M.D., Ph.D., assistant professor of pediatrics and of biomedical informatics and the study's senior author, and his colleagues looked at data from about six genome-wide association studies conducted on patients with or without autoimmune diseases including type 1 diabetes, rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, and ankylosing spondylitis.

    The investigators focused on the 573 SNPs that were examined in each of the six published studies. They found 15 that predisposed an individual to several autoimmune diseases. To their surprise, they found nine locations that conferred a heightened risk of certain autoimmune diseases but reduced risk of getting certain others.

    For instance, a particular chemical unit at an SNP site shown to predispose people to multiple sclerosis also rendered them, as a group, more likely to have autoimmune thyroid disease. On the other hand, an alternative chemical unit at the same site predisposed them to rheumatoid arthritis and ankylosing spondylitis. Additionally, people predisposed to one pair of diseases were protected against the other.

    “Maybe we should stop considering all autoimmune diseases in one lumped category,” remarks Dr. Butte, who is also the director of the Center for Pediatric Bioinformatics at Lucile Packard Children's Hospital. “It looks as if there may be at least two different kinds.

    “Several of these nine interesting SNPs we've found are located in or near genes that code for molecules found on cell surfaces,” Dr. Butte continues, making them potentially easier targets for drug development.

     



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