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遗传多态性在年轻心肌梗死中的作用。

Role of genetic polymorphisms in myocardial infarction at young age.

机构信息

Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Università degli Studi di Palermo, Palermo, Italy.

出版信息

Clin Hemorheol Microcirc. 2010;46(4):291-8. doi: 10.3233/CH-2010-1353.

Abstract

Acute myocardial infarction (AMI) in young adult presents a typical pattern of risk factors, clinical, angiographic and prognostic characteristics. In the last years we demonstrated that hemorheological profile is altered in these patients in a persistent way and independently of the number of risk factors and of the extent of coronary lesions. Thus, the hyperviscosity syndrome following AMI could be considered an intrinsic characteristic of these patients. Consequently it is possible to hypothesise the presence of a genetic background at the origin of this predisposition. If this background is able to influence the risk of ischemic heart disease, this should be particularly evident in young subjects. Since inflammatory mechanisms play a central role in mediating all phases of atherosclerosis, genes encoding for inflammatory or anti-inflammatory molecules are candidates for the risk of developing atherosclerosis. As atherosclerosis is the first cause of mortality in Western countries and if pro-inflammatory genotypes contribute to risk of coronary heart disease, alleles associated to disease susceptibility should not be included in the genetic background favouring longevity: People genetically predisposed to a weak inflammatory activity have fewer chances to develop cardiovascular disease and, therefore, have better chance for a long-life. According to this hypothesis, we studied in our population of young patients with AMI, the distribution of some polymorphisms influencing a inflammation and found an higher prevalence of pro-inflammatory polymorphisms (SNP A2080G of pyrin gene, SNP Gly670Arg of PECAM gene, C1019T of Cx 37 gene, SNP G1059C of PCR gene) and a lower prevalence of anti-inflammatory polymorphisms (Asp299Gly of TLR4 gene, SNP -1082 G/A of IL10 gene, CCR5Δ32). Results of these studies show that early myocardial infarction could be associated with a genetic predisposition to an intense inflammatory response, associated also to an hyperviscosity syndrome.

摘要

急性心肌梗死(AMI)在年轻成人中呈现出典型的危险因素、临床、血管造影和预后特征模式。近年来,我们证明了这些患者的血液流变学特征发生了持续变化,并且独立于危险因素的数量和冠状动脉病变的程度。因此,AMI 后出现的高粘血症综合征可以被认为是这些患者的固有特征。因此,可以假设这种易感性的发生与遗传背景有关。如果这种背景能够影响缺血性心脏病的风险,那么在年轻患者中应该更为明显。由于炎症机制在介导动脉粥样硬化的所有阶段中起着核心作用,因此编码炎症或抗炎分子的基因是导致动脉粥样硬化风险的候选基因。由于动脉粥样硬化是西方国家死亡的首要原因,如果促炎基因型增加了患冠心病的风险,那么与疾病易感性相关的等位基因不应包含在有利于长寿的遗传背景中:遗传易感性较弱的炎症活性的人患心血管疾病的机会较少,因此长寿的机会更大。根据这一假设,我们在 AMI 的年轻患者群体中研究了一些影响炎症的多态性的分布,发现促炎多态性(pyrin 基因的 SNP A2080G、PECAM 基因的 SNP Gly670Arg、Cx37 基因的 C1019T、PCR 基因的 SNP G1059C)的患病率较高,抗炎多态性(TLR4 基因的 Asp299Gly、IL10 基因的 SNP -1082 G/A、CCR5Δ32)的患病率较低。这些研究结果表明,早期心肌梗死可能与强烈炎症反应的遗传易感性有关,也与高粘血症综合征有关。

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