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Chinese Han population MMP3, TM, TSP1 and TSP4 gene and coronary heart disease association studies

Author: ZhouXiaoYang
Tutor: GuDongFeng
School: Peking Union Medical College , China
Course: Population genetics and genetic epidemiology
Keywords: Coronary heart disease myocardial infarction single nucleotide polymorphism haplotype matrix metalloproteinase thrombomodulin thrombospondin
CLC: Q987
Type: PhD thesis
Year: 2004
Downloads: 104
Quote: 0
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Abstract


Background: Myocardial infarction (MI), one of the leading causes of death worldwide, is a complex disorder influenced by multiple genetic factors and environmental factors. Approximately 90% of MI results from an acute thrombus that obstructs an atherosclerotic coronary artery. Plaque rupture is considered to be the major trigger of coronary thrombosis. Although the mechanism underlying plaque rupture is unclear, it has been shown that lipid-rich plaques express higher levels of matrix metalloproteinase 3 (MMP3) than fibrotic plaques, and MMP3 may contribute to weakening of the cap and subsequent rupture. Over the past few years, several studies have found an association between MI and some polymorphisms in MMP3 gene, but others have not. This variability in results might be due to linkage relationships with other unidentified functional genetic variants in this gene, so the aim of the present study was to scan the whole MMP3 gene to identify all putative functional polymorphisms and further to investigate whether these polymorphisms are associated with MI in Chinese Han population. In addition, a recent American study indicated that the TSP1 N700S and TSP4 A387P variants may be the new predictors for CHD/MI, and this discovery was listed within "AHA top 10 advances for 2001". Likewise, some studies showed that TM -33G/A appeared to associate with CHD/MI in Chinese Taiwanese. However, these findings remained controversial. In this study, we also further investigate whether these polymorphisms are related to CHD/MI in our population.Methods: a case-control design was applied in this study. In brief, a total of 817 unrelated CHD patients were enrolled from hospitalized patients, of Fu Wai Hospital and of Peking Union Medical College Hospital, between October 1997 and September 2000 who met the following criteria: prior suffered from acute MI, or documented by coronary angiography at least a 70% stenosis in a major epicardial artery. 847 subjects, age- and sex-matched, were randomly recruited from individuals participating in a community-based survey of cardiovascular risk factors in Beijing. A detail of

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