Identification of novel targets in scleroderma: update on population studies, cDNA arrays, SNP analysis, and
S Sohail Ahmed1, Filemon K Tan
1Department of Internal Medicine, University of Texas Medical School-Houston, Texas 77030, USA. sohail.ahmed@uth.tmc.edu
Purpose Of Review:
Systemic sclerosis, or scleroderma, is an uncommon autoimmune connective tissue disease that results in systemic fibrosis. Its etiologic basis remains unclear. The pathogenesis of systemic sclerosis involves a proliferative and obliterative vasculopathy resulting from endothelial cell dysfunction, extensive fibrosis secondary to fibroblast activation, and autoimmunity as demonstrated by the presence of disease-specific autoantibodies. Although there is no clear and convincing evidence for an environmental trigger in most cases, accumulating data emphasize the role of genetic factors in systemic sclerosis. As in other complex human diseases, multiple genes likely contribute to disease susceptibility and the clinical manifestations of systemic sclerosis. This review will cover the application of genomics to the complex genetics of systemic sclerosis.
Recent Findings:
The following review is an update on novel targets identified in scleroderma based on published reports (May 2000-May 2003) of mutation/polymorphism analysis (using SNP and haplotyping), the results from a recent genome-wide scan on a Native American population with systemic sclerosis, and gene expression studies (microarrays).
Summary:
The use of genomics has revealed novel targets and genetic associations that may contribute to the cause, the onset, and the subsequent pathologic changes that constitute systemic sclerosis. The identification of potential candidates for gene therapy or disease-specific targets amenable to pharmacologic intervention will benefit patients with systemic sclerosis who are currently being treated for their symptoms and not the disease process itself.
Insights
Genomics research is uncovering genetic factors contributing to systemic sclerosis (scleroderma). Identifying these genetic targets may lead to new therapies for this autoimmune disease.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease characterized by systemic fibrosis.
- Its exact cause is unknown, but involves vasculopathy, fibroblast activation, and autoimmunity.
- Genetic factors are increasingly recognized as significant contributors to disease susceptibility and manifestations.
Purpose of the Study:
- To review the application of genomics in understanding the complex genetic basis of systemic sclerosis.
- To highlight novel genetic targets and associations identified through recent research.
Main Methods:
- Analysis of mutation and polymorphism data (SNP, haplotyping).
- Genome-wide scans in affected populations.
- Gene expression studies using microarrays.
Main Results:
- Genomic studies have identified novel genetic associations relevant to systemic sclerosis.
- These findings offer insights into the disease's etiology, onset, and pathological progression.
- Specific genetic targets amenable to pharmacologic intervention are emerging.
Conclusions:
- Genomics has significantly advanced the understanding of systemic sclerosis genetics.
- Identification of genetic targets holds promise for developing disease-specific therapies.
- Future interventions may target the underlying disease process rather than just symptoms.
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