Auer Johann, Weber Thomas, Berent Robert, Lassnig Eliabeth, Lamm Gudrun, Eber Bernd
Department of Internal Medicine II, Division of Cardiology and Intensive Care, General Hospital Wels, Grieskirchnerstrasse 42, A-4600 Wels, Austria.
Am J Pharmacogenomics. 2003;3(5):317-28. doi: 10.2165/00129785-200303050-00003.
Both inflammation and genetics play an important role in the pathogenesis of atherosclerosis and coronary artery disease. Epidemiological studies have investigated the association between coronary artery disease (CAD) and gene polymorphisms of the inflammatory molecules tumor necrosis factors (TNF) alpha and beta, transforming growth factors (TGF) beta-1 and beta-2, interleukin (IL)-1 and its receptor antagonist (IL-1ra), CD14 (the receptor for lipopolysaccharide), P- and E-selectins, and platelet endothelial cell adhesion molecule (PECAM)-1. Current evidence suggests that the TNF polymorphisms explored so far are not linked to CAD. The majority of studies conducted showed no significant association between TGFbeta-1 and coronary atherosclerosis, but the data currently available are somewhat controversial. Some polymorphisms may increase the risk of myocardial infarction (MI) within specific ethnic groups or in certain populations. The association between the IL-1 system and atherosclerosis is complex and may vary as a result of a number of factors, such as stage of disease, clinical phenotype, and possibly population characteristics. The E-selectin gene (SELE) Arg128, 98T, and Phe554 alleles may increase the risk of atherosclerosis, but not necessarily the risk of MI. This association seems to be more pronounced in younger patients. The PECAM1 Leu125Val and Ser563Asn polymorphisms may increase the risk of atherosclerosis but not necessarily of MI. This association may be especially important in patients with a low risk for developing atherosclerosis. Current data indicate that screening for CD14-260C/T genotypes is unlikely to be a useful tool for risk assessment and it remains unclear whether CD14 polymorphisms significantly increase the risk of MI. The associations between candidate gene polymorphisms and CAD are complex as a consequence of pleiotropy, variations with age, selection due to the high lethality of the disease, and interactions with other genes and environmental factors. Nonetheless, although the current data is preliminary and partly conflicting, it does provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of CAD.
炎症和遗传因素在动脉粥样硬化和冠状动脉疾病的发病机制中均起着重要作用。流行病学研究调查了冠状动脉疾病（CAD）与炎症分子肿瘤坏死因子（TNF）α和β、转化生长因子（TGF）β-1和β-2、白细胞介素（IL）-1及其受体拮抗剂（IL-1ra）、CD14（脂多糖受体）、P-和E-选择素以及血小板内皮细胞黏附分子（PECAM）-1的基因多态性之间的关联。目前的证据表明，迄今为止所研究的TNF多态性与CAD并无关联。大多数研究表明，TGFβ-1与冠状动脉粥样硬化之间无显著关联，但目前可得的数据存在一定争议。某些多态性可能会增加特定种族群体或某些人群中心肌梗死（MI）的风险。IL-1系统与动脉粥样硬化之间的关联较为复杂，可能会因多种因素而有所不同，如疾病阶段、临床表型以及可能的人群特征等。E-选择素基因（SELE）的Arg128、98T和Phe554等位基因可能会增加动脉粥样硬化的风险，但不一定会增加MI的风险。这种关联在年轻患者中似乎更为明显。PECAM1的Leu125Val和Ser563Asn多态性可能会增加动脉粥样硬化的风险，但不一定会增加MI的风险。这种关联在动脉粥样硬化发病风险较低的患者中可能尤为重要。目前的数据表明，对CD14-260C/T基因型进行筛查不太可能成为一种有用的风险评估工具，而且目前尚不清楚CD14多态性是否会显著增加MI的风险。由于基因多效性、随年龄的变化、因疾病高致死率导致的选择以及与其他基因和环境因素的相互作用，候选基因多态性与CAD之间的关联较为复杂。尽管如此，虽然目前的数据是初步的且部分相互矛盾，但确实提供了一些证据表明炎症系统遗传学的改变可能会改变CAD的风险。
