Soutar A K
MRC Lipoprotein Team, Hammersmith Hospital, London, UK.
J Intern Med. 1992 Jun;231(6):633-41. doi: 10.1111/j.1365-2796.1992.tb01252.x.
Inherited defects in the gene for the low density lipoprotein (LDL)-receptor give rise to familial hypercholesterolaemia (FH), a disorder in which defective catabolism of LDL causes a marked increase in its concentration in plasma. As a result, there is excessive deposition of cholesterol in the arterial wall leading to accelerated atherosclerosis and premature coronary heart disease in most patients, although there are differences in its severity. Many different mutations have been found in the LDL receptor genes of FH patients, and although this heterogeneity has provided information about the relationship between structure and function in different domains of the protein, it makes simple DNA-based diagnosis of the disease impossible. When sufficient groups of patients with defined mutations are available it will be possible to determine the relative importance of any particular mutation compared with other genetic or environmental factors in relation to the severity of their symptoms or their response to treatment.
低密度脂蛋白（LDL）受体基因的遗传性缺陷会导致家族性高胆固醇血症（FH），在这种疾病中，LDL的分解代谢缺陷导致其在血浆中的浓度显著升高。因此，胆固醇在动脉壁中过度沉积，导致大多数患者动脉粥样硬化加速和冠心病过早发生，尽管其严重程度存在差异。在FH患者的LDL受体基因中发现了许多不同的突变，虽然这种异质性提供了有关该蛋白质不同结构域中结构与功能关系的信息，但却使得基于DNA的疾病简单诊断变得不可能。当有足够数量具有明确突变的患者群体时，就有可能确定任何特定突变与其他遗传或环境因素相比，在症状严重程度或对治疗反应方面的相对重要性。
