This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.OBJECTIVE: This is a clinical research project aimed at elucidating the demographic, clinical, serological, and genetic predictors of disease outcome in systemic sclerosis. The hypothesis to be tested is that systemic sclerosis is a more aggressive disease in non-Caucasians manifested by critical organ failure and a poor overall prognosis.RESEARCH PLAN: This is a component of the NIH funded SCOR for Scleroderma. The San Antonio component currently consists of 37 patients, largely Hispanic (defined as all 4 grandparents being Hispanic), diagnosed with scleroderma within the past five years. They are being studied longitudinally every six months to determine genetic, sociodemographic, and pertinent clinical and laboratory parameters that may predict disease outcome. The study will determine the HLA class II genotypes by DNA oligotyping and disease-associated alleles of other candidate genes found to be associated with SS; determine the sociodemographic parameters and behavioral features of the patients; determine pertinent clinical and laboratory parameters including disease manifestations; follow disease progression to outcomes; and examine the relative contributions and interactions of genetic, demographic, socioeconomic, cultural, familial, and initial clinical and laboratory features on the course and outcome of the disease. African Americans and Caucasian patients were enrolled at UT Medical Centers in Houston and Galveston.METHODOLOGY: Patients are seen and evaluated in the GCRC. Physical examination, routine laboratory procedures, and ECGs are performed every six months. Chest x-ray and pulmonary function tests are obtained yearly. Extensive questionnaires evaluating sociodemographic values, physical function, quality of life, social support, and attitudes toward health are administered every six months.CLINICAL
The scleroderma severity scale was scored for all patients. This included sociodemographic features, organ system manifestations including the Rodnan skin score, immunologic factors (ANA, antibodies to topo 1, centromere, fibrillarin, RNA polymerase I-III, Th/To, PM-Scl), HLA class II genes, and behavioral/psychosocial features. Data were analyzed using stepwise linear regression to identify significant independent risk factors for higher damage/severity scores. African-Americans have significantly higher damage scores compared to Caucasians (8.48 vs. 6.36 p=0.004) but not compared to Hispanics (7.32 p=0.2). Statistically significant factors included higher skin scores, lower income, public insurance, anti-U1-RNP antibodies, cytoplasmic ANA, HLA DQB1*05, lower hematocrit, and lower DLCO. This model is quite robust, accounting for 65% of the overall variance. Disease damage early in the course of scleroderma is influenced by a combination of lower sociodemographic status, skin involvement, and serologic and immunogenetic determinants.
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