University of Minnesota Researchers Find Gene Connected to Lupus Discovery May Lead to More Individualized Treatments for the Disease (April 16, 2006 - Washington, DC) The on-line journal, Nature Genetics, reports that Dr. Timothy W. Behrens, M.D., professor of medicine at the University of Minnesota and colleagues have identified a variant of a gene that is associated with lupus. The Lupus Foundation of America (LFA) is encouraged by this finding, as it offers additional insight into the underlying causes of this complex disease, which causes inflammation and tissue damage to virtually any organ system in the body.
Lupus is likely to be caused by the interaction of genetic and environmental factors. Although knowledge about the regions of chromosomes on which lupus genes seem to be located has been advancing, actual identification of genes that might contribute to this condition has been limited. This is because the genetics of lupus is highly complex with likely dozens of genes involved that will vary among different ethnic groups and among affected individuals within these groups. Thus, there will not be one gene found for lupus, but many that are likely to differ from person to person. The researchers studied DNA samples of lupus patients and healthy people (used as controls) from the United States, Spain, Sweden, and Argentina, looking for changes in the DNA sequence of a gene known as interferon regulatory factor 5 (IRF5). They identified a DNA variant that was found more frequently in lupus patients compared with the healthy people used as controls. Further experiments showed that this single change in the DNA sequence of IRF5 altered the way that the gene is expressed in cells of the immune system.
The gene the researchers identified plays a role in turning on a pathway in the body’s immune system that is meant to fight infection. In the case of people with lupus, this pathway is turned on and it doesn’t turn off.
The gene variation is common—50 percent of all people carry one copy of the gene variant and 25 percent carry two copies. Yet clearly not all people who carry the gene variant develop lupus. Dr. Gary Gilkeson, Professor of Medicine at the Medical University of South Carolina, is Chair of the LFA Medical-Scientific Advisory Committee. “The current finding by the Behrens group at the University of Minnesota is highly significant as it describes a change in a gene that is University of Minnesota Researchers Find Gene Connected to Lupus Page 2 of 2 common in the population, yet when present is highly associated with lupus.
By itself this genetic change is unlikely to cause lupus, but only when expressed with other genes in association with specific environmental triggers. "This gene (IRF5) plays a key role in the immune response as part of the interferon pathway. Previously Dr. Behrens group and others have observed that the interferon pathway is activated in many patients with lupus. Thus this new genetic finding provides a significant link between the clinical finding of interferon activity in lupus patients, and a possible genetic explanation for this activation. These findings suggest the possibility that therapies directed at balancing the effects of IRF5 might be useful in the treatment of lupus, although this is still speculative."
Due to the rapid developments in genetic screening techniques, this is likely only the first of many such significant genetic associations in lupus in the near future. The ultimate goal is to determine the "personal genetics of lupus" in each individual patient and then develop targeted therapies that address imbalances in the immune response that might occur in people with these genetic patterns.
"As treatments for disease become more personalized and tailored to an individual’s specific situation and genetic makeup, identifying carriers of this gene variant could be helpful in developing the most successful treatment plan," said Dr. Behrens.
The LFA estimates that approximately 1.5 million Americans have a form of lupus, mostly women. African Americans, Hispanics, Native Americans and Asians seem to be at greatest risk for developing lupus. For additional information about lupus, visit the LFA website at www.lupus.org, or call toll-free 1-888-38-LUPUS (888-385-8787) to request a free brochure.
The Lupus Foundation of America, headquartered in Washington, DC, is the nation’s leading nonprofit organization dedicated to finding the causes and cure for lupus. The LFA supports programs of research, education, patient services, and advocacy through its national office and a nationwide network of nearly 300 chapters, branches and support groups.
Link to the full text of the journal article.
Link to download a PDF of the paper
Dr. Timothy Behrens previously was the recipient of a $150,000 LFA research grant for a study entitled, "Mapping and Cloning of an SLE Susceptibility Gene on Human Chromosome 1."