From the Archives: Fall 2006 Issue of Lupus Now Magazine
Unraveling The Genetics Of Lupus
By Jennifer Pearce
Clinical Research Coordinator, Division of Rheumatology, University of California, San Francisco
When my husband and I considered starting a family, my lupus and the impact that pregnancy would have on my health was of great concern to us as well as my doctors. Of equal concern for me was the chance that I would pass genes on to my child that might predispose her to develop lupus or another autoimmune disease. My job as a study manager on the Lupus Genetics Research Project at the University of California, San Francisco served as a daily reminder that genes play a substantial role in determining who gets this disease.
Ultimately, it was the exposure to this research that convinced me that if my child developed lupus, her experience would be much different than mine. Thanks to dedicated researchers, advances in technology and, most important, the willingness of people with lupus to provide genetic samples, the next decade could bring significant improvements to the way people are diagnosed, treated, and live with lupus.
While environmental factors such as infections and stress may account for 35 percent of the risk of developing lupus, genes may contribute 65 percent of the risk. It is this combination of genes inherited from our mothers and fathers that, when exposed to something in the environment, causes lupus. Researchers have estimated that a relatively small combination of 10-30 "candidate" genes, out of a total 35,000, may play an important role in the development of the disease. It was with that knowledge that Lindsey Ann Criswell, M.D., started the Lupus Genetics Research Project in 1997 with the goal of examining candidate genes in people with lupus across all ethnic groups.
To date, more than 2,000 people with lupus have enrolled in Criswell's free studies, making them the largest group assembled for lupus genetics research. Thanks to new technologies that allow genetic material to be extracted from a small saliva sample, the entire study enrollment process takes place through the mail, giving participants across the country the opportunity to advance lupus research without ever leaving home.
One of Criswell's main goals is to gain a better understanding of how the disease can vary in terms of its severity, depending on a person's ethnic background. For example, lupus is three times more common in African-American women than in Caucasian women, and also more common in women of Hispanic/Latina, Asian, and American Indian descent. So far, her research confirms the significant role genes-and ethnicity-play in lupus, specifically in determining what complications patients might be predisposed to, or likely to develop in the future.
When examining the relationship between genes and kidney disease in lupus (lupus nephritis), doctors found a link between a group of gene variants and the severity of nephritis among Asians with lupus. A different type of gene demonstrated a similar increase in nephritis risk, but only for Caucasians. Another very recent study suggests that a particular gene variation produces different outcomes in different ethnic groups.
Collectively, these studies and the results they have already produced give me confidence as a woman with lupus and a mother. In the near future, researchers hope to translate this knowledge into faster, more accurate diagnoses; more certainty about which complications, if any, may develop over time; and improved treatments that work by targeting specific genes, potentially before the disease even starts. These are all reasons to be hopeful.