Charge Heterogeneity of LDL in Asymptomatic Hypercholesterolemic Men Is Related to Lipid Parameters and Variations in the ApoB and CIII Genes

Author:

Védie Benoit1,Jeunemaitre Xavier1,Mégnien Jean Louis1,Myara Isaac1,Trébeden Hélène1,Simon Alain1,Moatti Nicole1

Affiliation:

1. From the Laboratoire de Biochimie Appliquée, Faculté des Sciences Pharmaceutiques et Biologiques, Châtenay-Malabry (B.V., I.M., H.T., N.M.), and the Laboratoires de Biochimie (B.V., I.M., N.M.), Biologie Moléculaire (X.J.), and the Centre de Medecine Préventive Cardiovasculaire and INSERM U28 (J.L.M., A.S.), Hôpital Broussais, Paris, France.

Abstract

Abstract —This study was carried out to examine the relationship between the charge on low density lipoproteins (LDLs) and lipid and clinical parameters in 104 asymptomatic dyslipidemic men and to identify biochemical and genetic factors that could contribute to the charge variability of LDL. LDL charge heterogeneity was evaluated by relative electrophoretic mobility (REM) on preformed 0.5% agarose gels and by chromatographic quantification of a minor electronegative LDL subfraction designated LDL(−). The mean REM value for LDL was 0.147±0.016 and the mean LDL(−) subfraction percentage was 5.6±2.8%. Both were positively correlated with common atherosclerotic risk factors, especially total cholesterol [for REM, r =0.27, P <0.005; for LDL(−), r =0.28, P =0.008] and LDL cholesterol [for REM, r =0.27, P =0.007; for LDL(−), r =0.26, P =0.01)] levels, and REM was positively correlated with triglycerides ( r =0.27, P <0.005) and negatively with apoAI levels ( r =−0.30, P <0.002). The variations in LDL charge were not due to oxidation, as measured by the lag phase and binding to the LDL receptor. The results of the 2 methods used to measure LDL charge were significantly correlated and had some identical characteristics (eg, association with LDL apoCIII content and plasma triglyceride levels in borderline and IIb dyslipidemic subjects); these methods reflect different specific features of LDL charge. The percentage of LDL(−) was correlated positively with the LDL sialic acid content ( P <0.0001), whereas the REM was related to at least 2 distinct chromosomal loci. Multiple logistic analysis showed that individuals carrying minor alleles of Bsr DI ( P <0.05), apoCIII/ Sac I ( P <0.01), as well as the frequent allele of Xba I ( P <0.05) at the apoB and CIII gene loci had high REMs. This result suggests that LDL charge heterogeneity, which is positively correlated with the atherogenic lipid profile, is influenced by both genetic and biochemical factors.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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