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Scientists identify genes linked to lupus in women
Date:1/20/2008

WINSTON-SALEM, N.C. An international consortium of scientists has identified multiple genes that are linked to systemic lupus erythematosus, a devastating autoimmune disease that affects between 1 million and 2 million Americans. Reporting in Nature Genetics, the scientists also confirmed earlier findings linking lupus to several other genes highlighting the role that genetics plays in the disease.

These findings underscore that numerous genes, which are often immune-function related, contribute to the risk of developing lupus, said Carl D. Langefeld, Ph.D., senior author from Wake Forest University School of Medicine and co-director of the International Consortium for Systemic Lupus Erythematosus Genetics (www.SLEGEN.org).

These results suggest biologic pathways that help us understand the condition better and suggest additional genetic and non-genetic triggers, said Langefeld. In addition, they help delineate the genetic distinctions between rheumatoid arthritis, lupus and other autoimmune diseases, which could lead to earlier, more accurate diagnoses.

Systemic lupus can involve the joints, kidneys, heart, lungs, brain and blood. The disease occurs in about 31 out of every 100,000 people and affects women nine times more frequently than men. Scientists believe that lupus is caused by genetic variants that interact with each other and the environment.

The current study was made possible because of advances in technology that allow researchers to take a more systematic approach to looking at the entire genome. It was supported by the Alliance for Lupus Research and the National Institutes of Health.

The researchers studied the DNA of 720 women of European descent with lupus and 2,337 women without lupus. They scanned the entire genome for more than 317,000 single nucleotide polymorphisms (SNPs), which are locations on chromosomes where a single unit of DNA, or genetic material, may vary from one person to the next. The goal was to identify SNPs linked to lupus. They confirmed these results in another independent set of 1,846 women with lupus and 1,825 women without lupus.

The scientists found evidence of an association with multiple SNPs in three genes: ITGAM, KIAA1542 and PXK, and also at SNP rs10798269, which is not within any known gene. ITGAM is important for both the adherence of immune cells and for cleaning up pathogens. KIAA1542 is important for translating the DNA code into proteins. PXK encodes a molecule that transmits signals and controls complex processes in cells. These scientists also found association in genes previously associated with lupus and other autoimmune diseases.

The scientists are now focusing their attention on specific pathways and genes identified in this study, trying to dissect the precise molecular mechanisms by which these genes contribute to the risk for lupus. Genetic factors likely predict specific complications or patterns of complications. If so, it might be possible to intervene earlier in the process to delay or prevent their onset.

This initial, important discovery will prove invaluable to all those affected by lupus, said Barbara Boyts, president of the Alliance for Lupus Research, which supported the study and continues to support SLEGENs efforts to uncover genetic information about lupus. We are hopeful that this information will lead to new and better treatment possibilities and, eventually, a cure for lupus.

Lupus is a decimating illness, said John Harley, M.D., Ph.D., lead author and SLEGEN director, from the Oklahoma Medical Research Foundation. As researchers, our goal is to reduce the burden of suffering caused by this disease. These findings have opened many new doors, and were excited to investigate whats inside each of them.


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Contact: Karen Richardson
krchrdsn@wfubmc.edu
336-716-4453
Wake Forest University Baptist Medical Center
Source:Eurekalert

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