Affiliation:
1. From Center E. Grossi Paoletti (L.C., A.C., I.F., I.E., G.F.), Department of Pharmacological Sciences, University of Milano; Department of Internal Medicine (L.P., M.R., S.B.), University of Genova; Department of Internal Medicine (P.A., G.B.B.), S. Giovanni e Paolo Hospital, Venezia; Department of Clinical and Applied Medical Therapy (M.A., A.M.), University of Roma “La Sapienza”; Departments of Nephrology (G.B.) and of Pathology (S.P.), Santa Maria della Misericordia Hospital, Udine; Department of...
Abstract
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-β 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 HDL
3
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine