A UCSF researcher has launched a cross-generational study to identify the genes that are linked to a potentially fatal disease that strikes up to 10 times as many women as men and a disproportionately high percentage of African-Americans and Hispanics.

Lindsey Criswell, MD, MPH, assistant professor of medicine, is seeking 750 patients who have been diagnosed with lupus, a disease causing skin rashes and aching joints in mild forms and leading to irreversible kidney damage and stroke in very severe cases.

Genetic factors probably play a major role in the increased susceptibility of ethnic minorities, according to Criswell. African-American women, for example, are not only more prone to lupus, they are more likely to suffer an aggressive form of the disease, she explains. Consequently, researchers are actively enrolling individuals from all ethnic backgrounds in order to study this phenomenon.

Lupus is one of the most serious of the autoimmune diseases, so-called because a person's immune system attacks his or her own body tissues. Lupus affects one in 2,000 Americans, but this figure is significantly higher for women of childbearing age. After menopause the risk tailspins, suggesting that female hormones play a significant role in disease incidence. Pregnancy and delivery have also been identified as periods when women are more vulnerable to lupus.

In men, lupus may more likely be the result of taking drugs to treat hypertension and irregular heart rhythms. But only a very small percentage of people taking these medications develop lupus and symptoms usually fade when the drugs are discontinued. Patients suffering from drug-induced lupus are excluded from the study.

Criswell is studying 10 "candidate genes"--genes that may predispose an individual to the disease. Participants must have at least one parent willing to undergo a simple procedure in order for researchers to compare DNA results. Parents of participants will be asked to do a self-administered buccal smear test--obtained by running a soft brush along the inside of the mouth--which can be mailed to researchers. Participants are also asked to complete a questionnaire and allow researchers to review their medical records.

Current treatments for lupus include anti-inflammatories, corticosteroids, and drugs that suppress the immune system for serious cases of the disease. While many patients respond well to these drugs, their prolonged use has been associated with a variety of serious side-effects such as kidney disease, cataracts, osteoporosis and an increased risk of certain cancers in the case of the immunosuppressants.

Criswell hopes the study leads to the development of better drugs to treat lupus.

"The inadequacies of current therapies for lupus stem largely from our lack of understanding about the underlying causes of the disease. We hope that by defining the genetic determinants of this serious illness, safer, more effective drugs will eventually become available.

"While every autoimmune disease has its unique traits, all share common features. We would anticipate that a clearer understanding of the genetic causes of lupus would pave the way to a better understanding of other autoimmune diseases such as rheumatoid arthritis," she says.

Lupus patients interested in participating in the study should contact Jennifer Bardsley, the project manager, at 415/502-7775, or toll-free at 888/223 3067.

By Suzanne Leigh

1st appeared 11/05/97

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