Bruckert E, Chapman J
Service d'endocrinologie-métabolisme, INSERM Unité 321, Paris.
Rev Prat. 1994 May 15;44(10):1287-93.
Familial hypercholesterolaemia is the most frequent of the monogenic genetic disorders. The studies of Brown, Goldstein and collaborators have facilitated decisive progress in our understanding of the pathophysiology of this hypercholesterolaemia, and more specifically in our knowledge of the metabolism of the low-density lipoproteins (LDL) and of cholesterol at the cellular level. Indeed, they have documented the existence of a ubiquitous receptor which facilitates cellular uptake of LDL-cholesterol; such cholesterol is subsequently available to satisfy the metabolic requirements of the cell. The description of numerous mutations of the LDL receptor protein have allowed an exemplary approach to the study of the relationship between its structure and function. Familial hypercholesterolaemia represents a classical illustration of the atherogenic role of LDL-cholesterol in a clinical context in man. This disorder has already featured three minor therapeutic revolutions: LDL apheresis, inhibitors of HMG-CoA reductase (statins) and most recently, gene therapy.
家族性高胆固醇血症是最常见的单基因遗传病。布朗、戈尔茨坦及其合作者的研究推动了我们对这种高胆固醇血症病理生理学理解的决定性进展，更具体地说，是在我们对低密度脂蛋白（LDL）代谢以及细胞水平胆固醇代谢的认识方面。事实上，他们证实了一种普遍存在的受体的存在，该受体促进细胞摄取LDL胆固醇；随后这些胆固醇可用于满足细胞的代谢需求。对LDL受体蛋白众多突变的描述为研究其结构与功能之间的关系提供了典范方法。家族性高胆固醇血症是LDL胆固醇在人类临床环境中致动脉粥样硬化作用的经典例证。这种疾病已经经历了三次小的治疗变革：LDL血液分离术、HMG - CoA还原酶抑制剂（他汀类药物），以及最近的基因治疗。
