Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and immune complex mediated glomerulonephritis. African- Americans have a three-fold increased incidence of SLE, more frequently develop nephritis, more frequently progress to renal failure and have increased mortality compared to whites. The worse prognosis in African-Americans may represent a generalized predisposition towards renal failure following any renal injury rather than being lupus specific. Environmental exposures such as smoking and exposure to occupational or environmental agents (i.e., lead, mercury, silica) may affect the development and progression of lupus nephritis. Our central hypothesis is that there are specific genetic factors that interact with environmental exposures leading to progressive renal disease in African-Americans with lupus. The Carolina Lupus Study includes 265 SLE patients who were diagnosed between January 1, 1995 and July 31, 1999. This cohort of patients provides an opportunity to examine renal disease and its progression in African- American SLE patients matched with appropriate population based controls. The Gullah population lives on the sea islands of South Carolina. They are unique in their genetic homogeneity with minimal Caucasian admixture (<5%). A large ongoing study of diabetes (Sea Island Project) in this population has established a working framework onto which we propose to piggyback studies of SLE. Using these unique cohorts of patients and controls, we propose the following specific aims to address our hypothesis: 1) Determine the development and progression of renal disease in CLU patients in relation to specific genetic factors. We will assess if genes linked with renal disease in hypertension and diabetes in African-Americans are associated with development and/or progression of renal disease in lupus. 2) Determine the risk of development and progression of lupus nephritis in CLU patients in relation to comorbid conditions (hypertension, diabetes), measures of socioeconomic status and/or modifiable environmental factors that have been associated with other forms of renal disease. 3) Perform pilot studies in the unique genetically homogenous Sea Island African-American Gullah population to assess the presence of lupus multiplex families, the prevalence of the genetic polymorphisms being assayed in Aim 1 and determine the prevalence of ANA positivity compared to control African- American cohorts.