Gene Expression as Predictors of Outcome in the GENISOS (Genetics vs Environm

University Of Texas Hlth Sci Ctr Houston, Houston TX

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Abstract

Systemic sclerosis (SSc) is a chronic disease characterized by fibrosis, vascular damage, and autoimmune[unreadable] phenomena. The etiology is unknown and the clinical spectrum is highly variable. Our study HYPOTHESIS is[unreadable] that prognosis in SSc can be predicted by gene expression profiling correlated with clinical, serologic and[unreadable] genetic/ethnic factors as well as sociodemographic features. Our SPECIFIC AIMS are as follows: 1) To[unreadable] perform classification analysis of peripheral blood gene-expression-profiles and skin biopsies from patients[unreadable] with early limited SSc, early diffuse SSc and matched healthy controls; 2) To compare these profiles in blood[unreadable] and skin biopsies from patients in the stable chronic phase of diffuse SSc to profiles from early, diffuse SSc[unreadable] both longitudinally (within individual patients) and in cross-sectional fashion (between separate patient[unreadable] groups); 3) to expand the multi-ethnic (Caucasian, Hispanic, and African-American) GENISOS early-disease[unreadable] SSc cohort following subjects longitudinally for disease relevant outcomes: 4) to characterize the cohort[unreadable] according to demographics, racial-ethnic background, clinical disease features, autoantibody subsets, HLA[unreadable] and other genetic testing, and socio-behavioral features; 5) To develop a model using the data from aims 1[unreadable] through 4 to identify subsets of patients and predict prognosis; and 6) to provide clinical material from this[unreadable] cohort to support Project 1 of this CORT. DESIGN and METHODS: SSc patients with <5 years of disease[unreadable] will be enrolled and followed at defined intervals using standardized forms. Serial blood samples will be[unreadable] obtained on all and skin biopsies will be done on some participants. Custom printed 50-oligonucleotide[unreadable] microarrays representing 19,700 human and 208 Arabidopsis (negative controls) genes will be used and[unreadable] supervised methods and class comparison will be used to discover differentially regulated genes between[unreadable] predefined classes (e.g., early diffuse SSc vs late diffuse SSc).GEE analysis will be used to examine the[unreadable] association between the outcomes (e.g..course of skin disease, pulmonary fibrosis, etc.) and independent[unreadable] variables (e.g., demographic, HLA, microarray data, etc.) LAY LANGUAGE SUMMARY: This project will[unreadable] study patients with the recent onset of scleroderma in order to identify features that distinguish those who[unreadable] will have mild disease from those who will have a more severe course. This information will help physicians[unreadable] and patients decide on a treatment plan that is appropriate for their level of disease.