Center E. Grossi Paoletti, Department of Pharmacological Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy.
J Clin Lipidol. 2012 May-Jun;6(3):244-50. doi: 10.1016/j.jacl.2012.01.006. Epub 2012 Jan 28.
Lecithin:cholesterol acyltransferase (LCAT) is responsible for cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia. Apolipoprotein B (apoB) is the main protein component of very-low-density lipoproteins and low-density lipoprotein (LDL). Mutations of APOB gene cause familial hypobetalipoproteinemia, a codominant disorder characterized by low plasma levels of LDL cholesterol and apoB.
This was a genetic and biochemical analysis of an Italian kindred with hypobetalipoproteinemia whose proband presented with hypoalphalipoproteinemia and severe chronic kidney disease.
Plasma lipids and apolipoproteins, cholesterol esterification, and high-density lipoprotein (HDL) subclass distribution were analyzed. LCAT and APOB genes were sequenced.
The proband had severe impairment of plasma cholesterol esterification and high preβ-HDL content. He was heterozygote for the novel LCAT P406L variant, as were two other family members. The proband's wife and children presented with familial hypobetalipoproteinemia and were heterozygotes for the novel apoB H1401R variant. Cholesterol esterification rate of apoB H1401R carriers was reduced, likely attributable to the low amount of circulating LDL. After renal transplantation, proband's lipid profile, HDL subclass distribution, and plasma cholesterol esterification were almost at normal levels, suggesting a mild contribution of the LCAT P406L variant to his pretransplantation severe hypoalphalipoproteinemia and impairment of plasma cholesterol esterification.
LCAT P406L variant had a mild effect on lipid profile, HDL subclass distribution, and plasma cholesterol esterification. ApoB H1401R variant was identified as possible cause of familial hypobetalipoproteinemia and resulted in a reduction of cholesterol esterification rate.
卵磷脂胆固醇酰基转移酶（LCAT）负责血浆中的胆固醇酯化。LCAT 基因突变导致家族性 LCAT 缺乏症，这是一种代谢紊乱，其特征是低α脂蛋白血症。载脂蛋白 B（apoB）是极低密度脂蛋白和低密度脂蛋白（LDL）的主要蛋白质成分。APOB 基因突变导致家族性低β脂蛋白血症，这是一种共显性疾病，其特征是 LDL 胆固醇和 apoB 血浆水平降低。
对意大利一个低β脂蛋白血症家族进行遗传和生化分析，先证者表现为低α脂蛋白血症和严重的慢性肾病。
分析血浆脂质和载脂蛋白、胆固醇酯化和高密度脂蛋白（HDL）亚类分布。测序 LCAT 和 APOB 基因。
先证者血浆胆固醇酯化和前β-HDL 含量严重受损。他是 novel LCAT P406L 变异的杂合子，另外两名家族成员也是如此。先证者的妻子和孩子患有家族性低β脂蛋白血症，是 novel apoB H1401R 变异的杂合子。apoB H1401R 携带者的胆固醇酯化率降低，可能是由于循环 LDL 量低所致。肾移植后，先证者的血脂谱、HDL 亚类分布和血浆胆固醇酯化率几乎恢复正常，提示 LCAT P406L 变异在其移植前严重低α脂蛋白血症和血浆胆固醇酯化受损中起轻度作用。
LCAT P406L 变异对血脂谱、HDL 亚类分布和血浆胆固醇酯化有轻度影响。apoB H1401R 变异被确定为家族性低β脂蛋白血症的可能原因，导致胆固醇酯化率降低。
