Sharifi Mahtab, Futema Marta, Nair Devaki, Humphries Steve E
Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK.
Department of Clinical Biochemistry, the Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK.
Curr Cardiol Rep. 2017 May;19(5):44. doi: 10.1007/s11886-017-0848-8.
Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation.
Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology is most likely, due to the co-inheritance of common LDL-C-raising variants. The cardiovascular presentation and management of FH will differ between patients based on their underlying genetic factors. New genotyping methods such as next-generation sequencing will provide us with better understanding of the genetic architecture of FH.
家族性高胆固醇血症（FH）是一种低密度脂蛋白胆固醇（LDL-C）的遗传性疾病，其特征是从出生起胆固醇水平升高，且患早发性冠心病的风险很高。在本文中，我们综述了FH的遗传基础及其对临床表现的影响。
已知三个基因（LDLR、APOB和PCSK9）中的任何一个发生突变都会导致常染色体显性遗传的FH，但在临床诊断为FH的患者中，只有约40%能检测到突变。其余患者很可能是多基因病因，这是由于常见的LDL-C升高变异共同遗传所致。FH患者的心血管表现和治疗将因其潜在的遗传因素而有所不同。新一代测序等新的基因分型方法将使我们更好地了解FH的遗传结构。
