OMRF discovers three new lupus genes

A massive effort led by OMRF scientists has identified three new lupus genes.

New research published in the April 6 issue of the American Journal of Human Genetics describes three lupus genes discovered by OMRF researchers as part of the largest study of its kind.

With help from partners around the world, including universities and research facilities in Granada, Spain, Taipei, Taiwan, Seoul, Korea, Bogota, Colombia, and across the U.S., OMRF scientists gathered more than 17,000 samples for large-scale genetic testing.

The project, which began in 2009, took a year to gather the samples and another year to run the genetic tests. Since then, the researchers have pored over the data, said the study’s lead author, and OMRF scientist Christopher Lessard, Ph.D.

“We have pinned down three new genes that show statistical significance for lupus risk,” he said. “We’ve also turned up another 11 regions we think might be related to lupus, but those need more study.”

“The study included a variety of ethnic groups, and the results show the genes that cause lupus aren’t always universal,” said Patrick Gaffney, M.D., who co-authored the study.

Using samples from a wide range of ethnic backgrounds, scientists found the genes IRF8 and TMEM39a were associated with lupus in European-American, African-American, Gullah and Asian patients. A third gene named IKZF3 was only significant in African-American and European-American samples.

Lupus is a chronic autoimmune disease caused by a combination of environmental and multiple genetic factors. The disease causes the immune system to become overactive, mistaking the body’s own cells like they were bacteria or viruses and attacking them. Symptoms include fatigue, fever, rashes and joint pain, and there is no known cure for the disease.

The massive international research effort has already turned up numerous other discoveries about lupus, said Gaffney. So far the project has resulted in at least 15 published papers, and several more are in the pipeline.

The next step will be studying the genes to find out what role they play in lupus, said Lessard.

“Identifying and characterizing these genetic risk factors in lupus will undoubtedly lead to improved diagnostics and therapeutics for this complex disease,” said OMRF scientist Kathy Moser, Ph.D., senior author of the new study.

Lupus Foundation of America, Oklahoma chapter Executive Director Mannix Barnes said the discovery marks another significant step for patients.

“The importance of continued research for lupus is imperative to finding the cause and treatments for a disease that affects over 1.5 million Americans, mostly women,” said Barnes. “I can honestly say from an executive viewpoint in an organization that fields thousands of calls annually from women affected by this disease, I hope research one day will be able to put us out of business and start saving lives in return.”

The research was funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, the Lupus Research Institute, the Alliance for Lupus Research, the Korean Healthcare Technology R&D Project, the Arthritis National Research Foundation Eng Tan Scholar Award, the Arthritis Foundation, the Swedish Research Council, the Swedish Association Against Rheumatism, the Fundacion Instituto de Salud Carlos III, the Wenner Gren Foundation, Arthritis Research UK, the Wellcome Trust, Kirkland Scholar Award, Wake Forest University Health Sciences Center for Public Health Genomics, the European Science Foundation, and the Federico Wilhelm Agricola Foundation Research grant.

OMRF scientists Courtney Montgomery, Ph.D., Marta Alarcon, Ph.D., Joan Merrill, M.D., Judith James, M.D., Ph.D., Hal Scofield, M.D., John Ice, M.D., Indra Adrianto, Ph.D., and Astrid Rasmussen, M.D., Ph.D. contributed to the study.