TY - JOUR
T1 - 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
T2 - An Italian case-control multicenter study on Lp(a)
AU - the Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsorders Control – ‘MIGHTY MEDIC.ORG’
AU - Stefanutti, Claudia
AU - Pisciotta, Livia
AU - Favari, Elda
AU - Di Giacomo, Serafina
AU - Vacondio, Federica
AU - Zenti, Maria Grazia
AU - Morozzi, Claudia
AU - Berretti, Daniele
AU - Mesce, Dario
AU - Vitale, Marco
AU - Pasta, Andrea
AU - Ronca, Annalisa
AU - Garuti, Anna
AU - Manfredini, Matteo
AU - Anglés-Cano, Eduardo
AU - Marcovina, Santica Marija
AU - Watts, Gerald Francis
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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).
AB - 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).
KW - Cholesterol loading capacity
KW - Genetic polymorphisms
KW - Genetics
KW - HyperLp(a)
KW - Lipoprotein apheresis
KW - Particle size
UR - http://www.scopus.com/inward/record.url?scp=85088785997&partnerID=8YFLogxK
U2 - 10.1016/j.jacl.2020.05.002
DO - 10.1016/j.jacl.2020.05.002
M3 - Article
C2 - 32718857
AN - SCOPUS:85088785997
SN - 1933-2874
VL - 14
SP - 487-497.e1
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 4
ER -
