Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a).
Cholesterol loading capacity
Genetic polymorphisms
Genetics
HyperLp(a)
Lipoprotein apheresis
Particle size
Journal
Journal of clinical lipidology
ISSN: 1933-2874
Titre abrégé: J Clin Lipidol
Pays: United States
ID NLM: 101300157
Informations de publication
Date de publication:
Historique:
received:
08
10
2019
revised:
06
05
2020
accepted:
08
05
2020
pubmed:
29
7
2020
medline:
7
8
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).
Sections du résumé
BACKGROUND
Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking.
OBJECTIVE
The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a).
METHODS
We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA.
RESULTS
Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).
Identifiants
pubmed: 32718857
pii: S1933-2874(20)30083-0
doi: 10.1016/j.jacl.2020.05.002
pii:
doi:
Substances chimiques
Lipoprotein(a)
0
Protein Isoforms
0
Cholesterol
97C5T2UQ7J
Apoprotein(a)
EC 3.4.21.-
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
487-497.e1Informations de copyright
Copyright © 2020. Published by Elsevier Inc.