Objective- To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metab. through the genetic and biochem. 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 Nephrol. throughout Italy. DNA anal. 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-d. lipoprotein cholesterol, and pre-? high-d. lipoprotein (LDL) were elevated, and high-d. lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concn., 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.

The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families / L. Calabresi, L. Pisciotta, A. Costantin, I. Frigerio, I. Eberini, P. Alessandrini, M. Arca, G. Bittolo Bon, G. Boscutti, G. Busnach, G. Frasca, L. Gesualdo, M. Gigante, G. Lupattelli, A. Montali, S. Pizzolitto, I. Rabbone, M. Rolleri, G. Ruotolo, T. Sampietro, A. Sessa, G. Vaudo, A. Cantafora, F. Veglia, S. Calandra, S. Bertolini, G. Franceschini. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 25:9(2005), pp. 1972-1978.

The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families

L. Calabresi
Primo
;
I. Eberini;G. Franceschini
Ultimo
2005

Abstract

Objective- To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metab. through the genetic and biochem. 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 Nephrol. throughout Italy. DNA anal. 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-d. lipoprotein cholesterol, and pre-? high-d. lipoprotein (LDL) were elevated, and high-d. lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concn., 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.
Familial lecithin:cholesterol acyltransferase deficiency; Fish eye disease; High-density lipoproteins; Lecithin:cholesterol acyltransferase; Mutation
Settore BIO/14 - Farmacologia
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/11460
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