OUTCOME OF SLE IN MINORITIES--NATURE VS NURTURE

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A growing body of data suggests that genetic factors, particularly genes of the major histocompatibility complex, impact on the course and prognosis of rheumatic diseases. Likewise, recent work attests to the importance of socioeconomic factors in the outcome of these disorders. Systemic Lupus Erythematosus (SLE) is a disease of great variability whose prevalence, morbidity, and mortality have been found to be higher in minority groups. This proposal seeks to explore the factors underlying higher morbidity in minority groups with SLE by examining the relationship of socioeconomic, demographic, cultural, immunogenetic, and clinical variables to early outcome in an inception cohort study of Hispanic, African-American, and Caucasian SLE patients from 2 geographical areas (Houston, TX and Birmingham, AL). Since most genetic studies on SLE have focused on Caucasians of European ancestry, findings have been limited by linkage disequilibrium within this relatively homogeneous racial group. Therefore, HLA class II genotypes (HLA-DRB1, DRB3, DRB5, DQA1, DQB1 and DPB1 alleles) will be determined by oligotyping as well as gene dosage thereof, and class III C4 and C2 protein allotypes will be determined in each of 80 Hispanics, 80 African- American and 80 Caucasians consecutively enrolled into the study. The examination of SLE across different racial and ethnic groups not only allows us the opportunity to better determine the role of specific genes in the pathogenesis of SLE, but allows the unique opportunity to examine other factors differentially related to ethnicity - such as health care behavior, compliance, education, and comorbidities - to determine the interplay of genetic and socio-cultural factors in the outcome of SLE in both minority and non-minority groups. Patients with 5 years or less of disease duration will be recruited from the existing lupus registries at the University of Alabama at Birmingham (UAB) and the University of Texas Health Sciences Center (UTHSC) at Houston which are being expanded to insure complete case ascertainment. Hispanic patients will be recruited at UTHSC (and UT Medical Branch at Galveston) whereas African-American and Caucasian patients will be recruited at both UAB, and UTHSC. Outcome measures will be evaluated biannually for three years. The outcomes to be examined are sensitive to early change and include frequency and severity of flares, disease activity (SLAM) and severity (SLICC), and functional disability in addition to more traditional parameters such as renal survival and survival per se. This will be the first systematic study of Hispanics with SLE in the United States and the first to examine the interplay among genetic and socio-cultural factors in diverse racial and ethnic groups with SLE.