Biggart S, Chin D, Fauchon M, Cardew G, du Fou L, Harker N, Quinn E, Keller C, Vincent R, Mayne L
Cardiac Department, St. Thomas's Hospital, London, United Kingdom.
Clin Cardiol. 1998 Nov;21(11):831-6. doi: 10.1002/clc.4960211109.
The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD.
This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor beta 2 (TGF beta 2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD.
In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF beta 2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories.
The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF beta 2 gene was rare and not associated with early onset IHD.
导致缺血性心脏病（IHD）的遗传因素尚不清楚，多个基因可能独立或协同作用，增加IHD风险并影响其预后。血管紧张素转换酶（ACE）基因和载脂蛋白E（ApoE）基因已被分别证实与IHD风险相关。
本研究旨在探讨ACE基因和ApoE基因的多态性是否与早发性IHD相关。另外，还研究了在伤口修复和心脏发育中起作用的转化生长因子β2（TGFβ2）基因的多态性与早发性IHD的关系。
本研究共纳入101例IHD患者（男性发病年龄＜55岁，女性＜60岁）和100例经血管造影证实冠状动脉正常的对照者。通过聚合酶链反应扩增或Southern印迹法确定ACE、ApoE和TGFβ2基因的基因型，并与患者的临床和家族史进行比较。
患者组中ACE D等位基因的频率（0.475）显著低于对照组（0.59，p = 0.03），这是由于DD基因型患者数量减少（患者：24%为DD基因型，对照组：33%为DD基因型）。心源性猝死也与DD基因型相关。这些数据表明ACE D等位基因与致命结局有关。未发现DD基因型与心肌梗死风险、发病年龄、血管病变程度、家族史、高血压或高胆固醇血症之间存在关联。ApoE基因型分析显示与早发性IHD无关。没有证据表明ACE和ApoE基因型对早发性IHD风险有协同作用。TGFβ2基因的多态性罕见，与早发性IHD无关。
