Abstract
Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a strong predictor of atherogenicity. The serum concentrations of remnant-like particle triglyceride (RLPTG) and remnant-like particle cholesterol (RLPC) have been determined in a representative sample of the Czech MONICA study (n = 285). The relationship was investigated between remnant particle triglyceride/cholesterol concentrations and polymorphisms in the genes APOC3 (−482C→T/3238C→G), APOE (ε2/ε3/ε4), APOCI (−317-321ins), APOB (signal peptide), hepatic lipase (LIPE, −480C→T), and lipoprotein lipase (LPL, S447X). Univariate analysis showed significant effects on RLPTG associated only with the APOE genotype (P = 0.009), the APOC3 −482C→T genotype (P = 0.018), and the APOCI −317-321ins (P = 0.014) genotype and significant effects on RLPC with APOE (P = 0.01) and APOCI −317-321ins (P = 0.021). The raising effect of the APOE genotype for both remnant cholesterol and triglyceride was confined to the ε2/4 (n = 6) and ε4/4 (n = 3) groups, and thus when the ε2/4 group was omitted in order to analyze by allele (ε2+/ε3+/ε4+), significance was lost (P = 0.6). There was strong linkage disequilibrium between the APOE and APOCI alleles (χ2, P < 0.001) and a multivariate ANOVA of RLPTG with all three significantly associated variants as factors demonstrated that while the APOC3 −482C→T effect was independent of the others (P = 0.003), the APOCI −317-321ins and APOE effects were not. This was also true for the APOCI −317-321ins and APOE effects on RLPC. To assess whether APOE-CI effects on RLPC were independent of their effects on total cholesterol and triglyceride levels, multiple linear regression was used. Using multiple linear regression, it appeared that the APOE-CI effects on RLPC were independent of their effects on plasma cholesterol, but the effects of APOC3 and APOE-CI on RLPTG could not be separated from their effects on plasma Tg levels.Further characterization of this remnant particle phenotype and its genetic determinants may lead to a better understanding of its metabolism and contribution to atherosclerosis.
Highlights
Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a strong predictor of atherogenicity
Remnant lipoproteins are partially catabolized chylomicrons and very low density lipoproteins (VLDLs) that are depleted of triglycerides (TG) and enriched with cholesterol esters
Lipoprotein remnants and remnant-like particle cholesterol (RLPC) concentrations were found to be highly correlated with total VLDL- and intermediate density lipoprotein (IDL)-cholesterol and VLDL-TG but not with LDL-cholesterol or LDL-apoB levels [4,5,6]
Summary
Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a strong predictor of atherogenicity. It appeared that the APOE-CI effects on RLPC were independent of their effects on plasma cholesterol, but the effects of APOC3 and APOE-CI on RLPTG could not be separated from their effects on plasma Tg levels Further characterization of this remnant particle phenotype and its genetic determinants may lead to a better understanding of its metabolism and contribution to atherosclerosis.—Waterworth, D. The development of immunochemical assays for immunoseparation of remnant particles (using anti-apolipoprotein A-I [apoA-I] and antiapoB-100 antibodies) has allowed the specific isolation of these particles and determination of their triglyceride and cholesterol content [3, 4] These antibodies allow the removal of most of the apoB-containing lipoproteins (low density lipoprotein [LDL]/VLDL) and apoA-I-containing lipoproteins (chylomicrons and high density lipoprotein [HDL]), leaving behind chylomicron and VLDL remnants that are enriched in apoE. Lipoprotein remnants and remnant-like particle cholesterol (RLPC) concentrations were found to be highly correlated with total VLDL- and IDL-cholesterol and VLDL-TG but not with LDL-cholesterol or LDL-apoB levels [4,5,6]
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