Goldbourt U, Neufeld H N
Arteriosclerosis. 1986 Jul-Aug;6(4):357-77. doi: 10.1161/01.atv.6.4.357.
This review discusses the genetic factors in the development of arteriosclerosis and coronary heart disease (CHD). In several studies, multivariate analysis of prospective mortality/morbidity data and angiographic findings have indicated that a family history of CHD contributed to CHD risk independently of the established risk factors. In addition, ethnic groups that differ in the prevalence and incidence of CHD also markedly differ in blood groups and protein-enzymatic markers. These or other genetic differences may affect CHD rates. Data from fraternal and identical twins, the source of some early genetic CHD findings, are reviewed. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as other monogenic disorders are discussed. The role of apoprotein E polymorphism i other monogenic disorders are discussed. The role of apoprotein E polymorphism in determining plasma LDL variability among individuals is considered. Recombinant DNA technology, molecular cloning, and the identification of restriction fragment length polymorphisms are new tools for investigators who assess DNA polymorphism. Recent advances in that domain include: DNA polymorphisms affecting blood levels of apo A-I and A-II, association of a DNA insertion on chromosome 19 with severe premature atherosclerosis, and information concerning linkage of the genes for various apolipoproteins. In addition, the evidence for a major genetic component in diabetes mellitus and research into the genetic aspects of hypertension are reviewed. The male/female ratio in pathologically and epidemiologically assessed atherosclerosis may provide clues to the role of genetics. Early structural changes in the coronary artery intima are compatible with the ethnic and gender predilection. A key question in understanding underlying mechanisms in atherosclerosis is why coronary arteries are occluded in individuals whose other arterial systems are largely unaffected. The review concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on uncovering genetically determined differences in arterial wall response to blood flow. Subpopulations with different genetic risks may be identified, in which case universal preventive strategies might be replaced with specific ones.
本综述讨论了动脉粥样硬化和冠心病（CHD）发生发展过程中的遗传因素。在多项研究中，对前瞻性死亡率/发病率数据和血管造影结果进行的多变量分析表明，冠心病家族史独立于已确定的危险因素，增加了患冠心病的风险。此外，冠心病患病率和发病率不同的种族在血型和蛋白质酶标记物方面也存在显著差异。这些或其他遗传差异可能会影响冠心病的发病率。本文回顾了来自异卵双胞胎和同卵双胞胎的数据，这些数据是早期一些遗传性冠心病研究结果的来源。文中讨论了脂蛋白代谢和转运的遗传疾病，如家族性高胆固醇血症，以及其他单基因疾病。还讨论了载脂蛋白E多态性在其他单基因疾病中的作用。考虑了载脂蛋白E多态性在个体血浆低密度脂蛋白变异性测定中的作用。重组DNA技术、分子克隆以及限制性片段长度多态性的鉴定，为评估DNA多态性的研究人员提供了新工具。该领域的最新进展包括：影响载脂蛋白A-I和A-II血液水平的DNA多态性、19号染色体上的DNA插入与严重早发性动脉粥样硬化的关联，以及各种载脂蛋白基因连锁的相关信息。此外，还回顾了糖尿病主要遗传成分的证据以及高血压遗传方面的研究。病理和流行病学评估的动脉粥样硬化中的男女比例可能为遗传学的作用提供线索。冠状动脉内膜的早期结构变化与种族和性别偏好相符。理解动脉粥样硬化潜在机制的一个关键问题是，为什么在其他动脉系统基本未受影响的个体中，冠状动脉会发生阻塞。综述最后讨论了未来动脉粥样硬化遗传研究的方向和意义，重点是揭示动脉壁对血流反应的基因决定差异。可能会识别出具有不同遗传风险的亚人群，在这种情况下，通用的预防策略可能会被特定的预防策略所取代。
