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

Laura Calabresi, Livia Pisciotta, Anna Costantin, Ilaria Frigerio, Ivano Eberini, Paola Alessandrini, Marcello Arca, Gabriele Bittolo Bon, Giuliano Boscutti, Ghil Busnach, Giovanni Frascà, Loreto Gesualdo, Maddalena Gigante, Graziana Lupattelli, Anna Montali, Stefano Pizzolitto, Ivana Rabbone, Marina Rolleri, Giacomo Ruotolo, Tiziana SampietroAdalberto Sessa, Gaetano Vaudo, Alfredo Cantafora, Fabrizio Veglia, Sebastiano Calandra, Stefano Bertolini, Guido Franceschini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1972-1978
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Familial lecithin:cholesterol acyltransferase deficiency
  • Fish eye disease
  • High-density lipoproteins
  • Lecithin:cholesterol acyltransferase
  • Mutation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Calabresi, L., Pisciotta, L., Costantin, A., Frigerio, I., Eberini, I., Alessandrini, P., Arca, M., Bon, G. B., Boscutti, G., Busnach, G., Frascà, G., Gesualdo, L., Gigante, M., Lupattelli, G., Montali, A., Pizzolitto, S., Rabbone, I., Rolleri, M., Ruotolo, G., ... Franceschini, G. (2005). The molecular basis of lecithin: Cholesterol acyltransferase deficiency syndromes: A comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(9), 1972-1978. https://doi.org/10.1161/01.ATV.0000175751.30616.13