Human evidence that the Cystatin C Gene is implicated in focal progression of Coronary Artery Disease
Eriksson, Per, Deguchi, Hiroyuki, Samnegard, Ann, Lundman, Pia, Boquist, Susanna, Tornvall, Per, Ericsson, Carl-Goran, Bergstrand, Lott, Hansson, Lars-Olof, Ye, Shu and Hamsten, Anders (2004) Human evidence that the Cystatin C Gene is implicated in focal progression of Coronary Artery Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, (3), 551-557. (doi:10.1161/01.ATV.0000117180.57731.36).
Download
Full text not available from this repository.
Description/Abstract
Objective— Overexpression of elastolytic cysteine and aspartic proteases, known as cathepsins, is implicated in atherogenesis. The potential significance of imbalance in expression between cathepsins and their inhibitor cystatin C in cardiovascular disease has been highlighted by the demonstration of cystatin C deficiency in human atherosclerosis and abdominal aortic aneurysms.
Methods and Results— We identified and characterized physiologically relevant polymorphisms in the promoter region of the cystatin C gene that influence cystatin C production and used these polymorphisms as a tool to examine the significance of cystatin C in coronary atherosclerosis in vivo in humans. Seven polymorphisms, all in strong-linkage disequilibrium, were identified in the cystatin C gene, of which 2 promoter polymorphisms (-82G/C and -78T/G) were functional in vitro in electromobility shift and transient transfection assays. Genotyping of 1105 individuals (237 survivors of a first myocardial infarction before age 60 and 2 independent groups comprising a total of 868 healthy individuals) revealed that the plasma cystatin C concentration was significantly lower in carriers of the mutant haplotype. Furthermore, the mutant haplotype was associated with a higher average number of stenoses per coronary artery segment in unselected postinfarction patients (N=237) undergoing routine coronary angiography.
Conclusions— These results provide human evidence for an important role of cystatin C in coronary artery disease.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Keywords: | cystatin c, genetics, coronary artery disease, promoter, remodeling |
| Subjects: | R Medicine > R Medicine (General) Q Science > QP Physiology Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Human Genetics |
| Item ID: | 24695 |
| Date Deposited: | 04 Apr 2006 |
| Last Modified: | 02 Mar 2012 11:26 |
| Contributors: | Eriksson, Per (Author) Deguchi, Hiroyuki (Author) Samnegard, Ann (Author) Lundman, Pia (Author) Boquist, Susanna (Author) Tornvall, Per (Author) Ericsson, Carl-Goran (Author) Bergstrand, Lott (Author) Hansson, Lars-Olof (Author) Ye, Shu (Author) Hamsten, Anders (Author) |
| Date: | 2004 |
| Status: | Published |
| Contact Email Address: | Shu.Ye@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/24695 |
Actions (login required)
 |
View Item |
