TY - JOUR
T1 - The molecular basis of lecithin
T2 - Cholesterol acyltransferase deficiency syndromes: A comprehensive study of molecular and biochemical findings in 13 unrelated Italian families
AU - Calabresi, Laura
AU - Pisciotta, Livia
AU - Costantin, Anna
AU - Frigerio, Ilaria
AU - Eberini, Ivano
AU - Alessandrini, Paola
AU - Arca, Marcello
AU - Bon, Gabriele Bittolo
AU - Boscutti, Giuliano
AU - Busnach, Ghil
AU - Frascà, Giovanni
AU - Gesualdo, Loreto
AU - Gigante, Maddalena
AU - Lupattelli, Graziana
AU - Montali, Anna
AU - Pizzolitto, Stefano
AU - Rabbone, Ivana
AU - Rolleri, Marina
AU - Ruotolo, Giacomo
AU - Sampietro, Tiziana
AU - Sessa, Adalberto
AU - Vaudo, Gaetano
AU - Cantafora, Alfredo
AU - Veglia, Fabrizio
AU - Calandra, Sebastiano
AU - Bertolini, Stefano
AU - Franceschini, Guido
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
KW - Familial lecithin:cholesterol acyltransferase deficiency
KW - Fish eye disease
KW - High-density lipoproteins
KW - Lecithin:cholesterol acyltransferase
KW - Mutation
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U2 - 10.1161/01.ATV.0000175751.30616.13
DO - 10.1161/01.ATV.0000175751.30616.13
M3 - Article
C2 - 15994445
AN - SCOPUS:24144480542
VL - 25
SP - 1972
EP - 1978
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -