人类枯草溶菌素转化酶9基因影响胆固醇代谢的研究进展

家族性高胆固醇血症(FH)是一种由低密度脂蛋白受体(LDLR)缺陷所导致的、以血总胆固醇升高为特征的常染色体显性遗传病.目前普遍认为FH是复杂的多基因病.近年研究发现,人类枯草溶菌素转化酶9(PCSK9)在血胆固醇代谢中起重要作用.一些PCSK9突变可减少LDLR总量,进而导致FH.而另一些PCSK9突变影响自身活性,导致低胆固醇血症.本文就PCSK9的基因结构、功能以及该基因不同突变体影响血胆固醇代谢的最新研究进展作一综述.

Investigation progress of proprotein convertase subtilisin/kexin type 9 influencing the metabolism of cholesterol

Familial hypercholesterolemia(FH) is a common autosomal dominant dyslipidemia,which is caused by mutations of the low-density lipoprotein receptor(LDLR) gene producing defect or deficiency in LDLR.The characters of FH are elevated level of total and LDL cholesterol.FH is considered to be a complex polygenic disease.Recently,more findings indicate that proprotein convertase subtilisin/kexin type 9(PCSK9) gene play an important role in serum cholesterol metabolism.Some mutated PCSK9 proteins decrease LDLR,which cause FH in affected families.Some other mutated PCSK9 proteins decrease self-affinity,which cause hypocholesterolemia.We review the newest researches about the structure,function ofPCSK9 gene and the relation of its mutations with plasma cholesterol metabolism.