Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity. It is a collagen-related disorder induced by betel quid chewing, a habit that is common in Taiwan. However, the cumulative exposure to betel quids varies in OSF patients. It seems that there is individual susceptibility to betel quid-induced OSF. This study compared the association of OSF and polymorphisms of six collagen-related genes, collagen 1A1 and 1A2 (COL1A1 and COL1A2), collagenase-1 (COLase), transforming growth factor beta1 (TGF-beta1), lysyl oxidase (LYOXase), and cystatin C (CST3), between patients with low and high exposure to betel quids. A total of 166 patients with OSF from a medical center and 284 betel quid chewers who were free of OSF and oral cancer, from the same hospital and five townships, were recruited. PCR-based restriction fragment length polymorphism assays were used to determine the genotypes of the six collagen-related genes situated on different chromosomes. We found that the genotypes associated with the highest OSF risk for collagen 1A1, collagen 1A2, collagenase-1, transforming growth factor beta1, lysyl oxidase, and cystatin C were CC, AA, TT, CC, AA, and AA, respectively, for the low-exposure group, and TT, BB, AA, CC, GG, and AA, respectively, for the high-exposure group. A trend was noted for an increased risk of OSF with increasing number of high-risk alleles for those with both high and low exposures for betel quid. The cell selection mechanism of oral fibroblasts is proposed to explain the effect of the modification of cumulative betel quid exposure on the risk profiles of collagen-related genes. These results imply that susceptibility to OSF could involve multigenic mechanisms modified by the betel quid-exposure dose.
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PMID:Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. 1210 Nov 12

Oral Submucous Fibrosis (OSF) is a chronic disorder characterized by fibrosis of the mucosa lining the upper digestive tract involving the oral cavity, oro- and hypopharynx and the upper third of the oesophagus. The alkaloids from areca nut are the most important chemical constituents biologically, in producing this lesion. These chemicals appear to interfere with the molecular processes of deposition and/or degradation of extracellular matrix molecules such as collagen. Increased collagen synthesis or reduced collagen degradation have been considered as a possible mechanism in the development of the disease. Increased and continuous deposition of extracellular matrix may also take place as a result of disruption of the equilibrium between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMP). Arecoline a product of areca nut was found to elevate Cystatin C mRNA (CST3) and protein expression in a dose-dependent manner. Cystatin C expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Cross-links between the molecules are essential for the tensile strength of collagen fibres. These areas are resistant to attack by collagenases but can be attacked by a number of other serine and cysteine proteinases. CST3 encoding a cysteine proteinase inhibitor might contribute to the stabilization of collagen fibrils in OSMF. Treatment directed against Cystatin C may serve as a novel treatment for submucous fibrosis and also in preventing its transformation into malignancy.
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PMID:Cystatin C: Its role in pathogenesis of OSMF. 2573 18