The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes -: A comprehensive study of molecular and biochemical findings in 13 unrelated Italian families
The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes -: A comprehensive study of molecular and biochemical findings in 13 unrelated Italian families
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DOI：
10.1161/01.atv.0000175751.30616.13
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发表时间：
2005-09-01
影响因子：
8.7
通讯作者：
Franceschini, G
中科院分区：
文献类型：
--
作者：
Calabresi, L;Pisciotta, L;Franceschini, G
目的-通过对携带LCAT基因突变的家族进行遗传和生化表征，更好地了解卵磷脂：胆固醇酰基转移酶（LCAT）在脂蛋白代谢中的作用。方法和结果-意大利脂质诊所和肾脏病科鉴定了13个携带17种不同LCAT基因突变的家族。对82名家庭成员进行DNA分析，发现15名LCAT突变等位基因携带者，11名患有家族性LCAT缺乏症（FLD）， 4名患有鱼眼病（FED）。44例携带1个突变LCAT等位基因，23例基因型正常。突变LCAT等位基因携带者的血浆未酯化胆固醇、未酯化胆固醇/总胆固醇比率、甘油三酯、极低密度脂蛋白胆固醇和β前高密度脂蛋白（LDL）升高，高密度脂蛋白（HDL）胆固醇、载脂蛋白a - i、载脂蛋白a - ii、载脂蛋白B、LpA-I、LpA-I: a - ii、胆固醇酯化率、LCAT活性和浓度、LDL和HDL3粒径以基因剂量依赖的方式减小。FLD和FED病例的脂质/脂蛋白谱没有差异，除了前者的血浆未酯化胆固醇和未酯化/总胆固醇比更高。结论：在大量携带LCAT基因突变的受试者中，LCAT基因型突变的遗传导致血浆脂质/脂蛋白谱的基因剂量依赖性改变，这在FLD或FED受试者之间非常相似。
Objective - To better understand the role of lecithin: cholesterol acyltransferase (LCAT) in lipoprotein metabolism through the genetic and biochemical characterization of families carrying mutations in the LCAT gene.Methods and Results - Thirteen families carrying 17 different mutations in the LCAT gene were identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11 with familial LCAT deficiency (FLD) and 4 with fish-eye disease ( FED). Forty-four individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides, very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I: A-II, cholesterol esterification rate, LCAT activity and concentration, and LDL and HDL3 particle size were reduced in a gene - dose-dependent manner in carriers of mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile of FLD and FED cases, except for higher plasma unesterified cholesterol and unesterified/total cholesterol ratio in the former.Conclusion - In a large series of subjects carrying mutations in the LCAT gene, the inheritance of a mutated LCAT genotype causes a gene - dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as FLD or FED.