An international consortium of scientists led by OMRF investigator John B. Harley, M.D., Ph.D., has identified multiple genes linked to lupus, a devastating autoimmune disease that affects as many as 2 million Americans and 15 million people worldwide. The group’s findings appear online in two related articles in the Feb. edition of the journal Nature Genetics.
The study identified 13 genes specifically associated with lupus. “Four of these are powerfully compelling, and the remainder warrant additional investigation,” Harley said. “By identifying the mechanisms of disease through basic research, as was done here, it can lead to fundamental understanding of the disease process and help us develop better therapies to fight it.”
The researchers studied the DNA of 720 women with lupus and 2,337 women without lupus. They scanned the entire genome of each subject, in each case examining 317,000 separate 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 those regions on the chromosome linked to the disease.
The scientists confirmed these results in another independent set of 1,846 women with lupus and 1,896 women without lupus. OMRF scientific staff analyzed all 3,671 specimens in their laboratories in Oklahoma City.
Lupus can affect any part of the body—most commonly the skin, joints, blood and kidneys—and can be life-threatening. 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.
In the new study, the scientists discovered a link with three genes previously thought unconnected to lupus. They also identified a link between the disease and a DNA region once believed to be “junk DNA”—a piece of genetic material without a known function. In addition, they uncovered further evidence of association for genes previously linked to lupus and other autoimmune diseases.
“Lupus is a decimating illness,” Harley said. “As clinical investigators, our goal is to reduce the burden of suffering caused by this disease. These findings have opened many new doors, and we’re excited to investigate what’s behind each of them.”
As head of OMRF’s arthritis and immunology research program, Harley has directed lupus genetics research in Oklahoma City for more than two decades. The new findings were made under his direction of the International Consortium for Systemic Lupus Erythematosus Genetics and were supported by the Alliance for Lupus Research and the National Institutes of Health.
“This initial, important discovery will prove invaluable to all those affected by lupus,” said Barbara Boyts, president of the Alliance for Lupus Research. “We are hopeful that this information will lead to new and better treatment possibilities and, eventually, a cure for lupus.”
A second Nature Genetics paper in the same issue by OMRF’s Swapan Nath, Ph.D., focused specifically on one gene on chromosome 16 and its relationship to lupus. Using data gathered from more than 4,000 patients, Nath and his colleagues determined that the gene likely plays a role in the disease and is present in 25 to 30 percent of lupus patients.
Through further studies, scientists hope to better understand the functional significance of this gene and its role in disease development. “By learning the genetic triggers for lupus, physicians may one day be able to provide each patient with treatment specifically targeted to their disease,” Nath said. “It may also open doors to earlier diagnosis as well as gene therapy for treating lupus.”
Other researchers in the project include OMRF’s Kathy Moser, Ph.D., Patrick Gaffney, M.D., Ken Kaufman, Ph.D., and Jennifer Kelly, as well as scientists from the University of Uppsala in Sweden, the Imperial College in London, the University of California at San Francisco, the University of Southern California, the University of California at Los Angeles, the University of Alabama at Birmingham, and Wake Forest University.
“This was an extraordinary effort, involving 150 scientists and staff and nearly 7,000 research volunteers,” said Harley. “The results promise to transform our understanding of lupus and to accelerate the day when safe and effective therapies are available.”
Individuals interested in volunteering for future lupus studies at OMRF should call 888-OK-LUPUS (888-655-8787). Both healthy individuals and those with a lupus diagnosis are encouraged to participate.