The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis
Abstract
During this second year of the project, we established multiple primary cell strains from normal controls and SSc patients. We performed stimulation assays with silica in 82 primary fibroblast strains. Our results showed that silica activate fibroblasts toward fibrotic changes. However, different fibroblast strains obtained from different individuals showed different responses in terms of the gene expression of the ECM components. Using longitudinal linear models in analysis of association between specific genotypes and dynamic changes of gene expression of the fibroblasts in responding to silica stimulation, we identified that specific SNPs were associated with either single gene expression, or paired gene expression such as CTGF/SPARC and COL1A2/COL3A1, which suggest a strong biological correlation between these genes. Moreover, some SNPs and/or their corresponding genes were found to be associated with both SSc susceptibility and the fibrotic changes of human fibroblast in response to silica stimulation. These SSc susceptibility genes include not only previously identified ones, but also some novel ones, such as HLA-DPB1 and APBA1. These observations supported our original proposal that genetic elements within SSc fibroblasts might contribute to susceptibility to fibrotic process. Integrative studies of genetic and environmental factors with human fibroblasts may facilitate the discovery of potential pathogenesis of SSc. In this year, we will continuously obtain more human fibroblasts, especially SSc fibroblasts. We also will continuously perform stimulation assays of newly obtained human fibroblasts for a better chance to identify genetic components inside SSc patients contributing to susceptibility to environmental stimuli. Meanwhile, we will try to explore which specific bio-pathways associated with which specific genetic factors involved in silica induced fibrotic changes. Therefore, our studies are fulfilled with original proposal in the grant.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA538691
Entities
People
- Xiaodong Zhou
Organizations
- University of Texas Health Science Center at Houston