Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and familial combined hypolipidemia
Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and familial combined hypolipidemia
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DOI：
10.1016/j.jacl.2017.06.013
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发表时间：
2017-10-01
影响因子：
4.4
通讯作者：
Arca, Marcello
中科院分区：
文献类型：
--
作者：
Di Costanzo, Alessia;Di Leo, Enza;Arca, Marcello
背景：低血浆胆固醇最常见的单基因原因是由于载脂蛋白B编码基因（APOB）的截短突变导致的家族性低脂蛋白血症（FHBL1）和由于ANGPTL3基因的功能缺失突变导致的家族性合并低血脂症（FHBL2）。目的：这两种情况的脂质表型的直接比较从未进行过。此外，尽管FHBL1中肝脏脂肪变性发生率的增加一直有报道，但FHBL2对肝脏的影响尚未得到很好的证实。方法：我们调查了350名受试者，67名APOB突变杂合子携带者，63名ANGPTL3 p.S17*突变携带者（57名杂合子和6名纯合子），以及220名非携带者的正常血脂对照。超声检查肝脂肪变性的发生率及程度。结果：从杂合子到纯合子FHBL2和FHBL1个体，低密度脂蛋白胆固醇水平稳步下降，其中携带APOB外显子1至25截断突变的杂合子FHBL1水平最低（趋势P < 0.001）。血浆甘油三酯水平在杂合FHBL1和纯合FHBL2个体中相似，但在杂合FHBL2个体中较高。高密度脂蛋白胆固醇水平在纯合子FHBL2中最低（P为趋势）
BACKGROUND: The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene.OBJECTIVE: A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established.METHODS: We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and 6 homozygotes), and 220 noncarrier normolipemic controls. Prevalence and degree of hepatic steatosis were assessed by ultrasonography.RESULTS: A steady decrease of low-density lipoprotein cholesterol levels were observed from heterozygous to homozygous FHBL2 and to FHBL1 individuals, with the lowest levels in heterozygous FHBL1 carrying truncating mutations in exons 1 to 25 of APOB (P for trend < .001). Plasma triglycerides levels were similar in heterozygous FHBL1 and homozygous FHBL2 individuals, but higher in heterozygous FHBL2. The lowest high-density lipoprotein cholesterol levels were detected in homozygous FHBL2 (P for trend