Genes Linked with Lupus Revealed
Posted 1/22/08
Lupus was a hot topic in the medical journals this week. Four different studies were released that identified genes related to lupus risk. One study appears in The New England Journal of Medicine and three others appear in Nature Genetics, all published online on January 20. A fifth study identified a genetic mutation that prevented the development of lupus in mice and was published in Immunity.
The findings published in Nature Genetics were the result of the work of the International Consortium for Systemic Lupus Erythematosus (SLEGEN). The consortium of scientists identified multiple genes linked to systemic lupus erythematosus, and underscore the importance of genetic variants in diseases that affect immune function.
SLEGEN Director John B. Harley, MD, PhD, explained that the study found strong evidence of association with multiple single nucleotide polymorphisms (SNPs) in three genes: ITGAM; KIAA1542; PXK; and at SNP rs10798269, a DNA unit not found within any known gene. SNPs are chromosome locations where a single unit of DNA may vary from one person to another.
The results also showed evidence linking lupus to nine other genes. "I would have been satisfied with finding one gene. The fact that we present 13 strong candidates, supported by data that are 99% accurate is tremendous,” said Harley. The variations may be linked to as many as 67 percent of all lupus cases in women. In the Nature Genetics study, the nine DNA variants helped to identify those who had up to twice the risk of getting lupus compared to those who did not have the variants.
The study published in the New England Journal identified two genetic variations linked to lupus: C8orf13-BLK and ITGAM-ITGAX. In an editorial accompanying the study, Mary K. Crow, MD, associate chief of the division of Rheumatology and director of Rheumatology research at Hospital for Special Surgery in New York, commented on the importance of the research. She was particularly intrigued by the research on ITGAM, whose association with lupus was supported by three of the new studies. The protein encoded by ITGAM is found on the immune system’s white blood cells that are recruited to blood vessels when it is activated. Some of the characteristic clinical features of lupus involve changes in blood vessels, including alterations in the kidneys, eyes, skin and the premature atherosclerosis that is common in lupus patients.
A study published in the January 18 edition of the journal Immunity identified a genetic mutation that prevented the development of lupus. The lupus-suppressing action is the result of what is known as a nonsense mutation of the Coronin-1A gene (Coro1a) required for the development of the disease. A nonsense mutation causes the gene to produce proteins that no longer function. “We were searching for a lupus susceptibility gene,” said lead study author Dwight Kono. “After mapping and cloning the Coronin-1A gene, we discovered this spontaneous mutation in a single strain of mice -- those that don’t get severe or systemic lupus-like disease. More than likely, the mutation had existed undetected in our mouse colony for years.”
All of these findings will ultimately lead to new therapies and earlier diagnosis of this devastating disease that affects an estimated 300,000 adult Americans.
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