Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster

• Published in: Journal of lipid research Vol. 41; no. 7; pp. 1103 - 1109
• Main Authors: Waterworth, D M, Hubacek, J A, Pitha, J, Kovar, J, Poledne, R, Humphries, S E, Talmud, P J
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.07.2000
• Subjects: Adult; apolipoprotein B; Apolipoproteins B - genetics; Apolipoproteins C - genetics; Apolipoproteins E - genetics; Arteriosclerosis - etiology; Cholesterol - blood; Chylomicron Remnants; Chylomicrons - blood; Coronary Disease - etiology; Czech Republic; Dietary Fats; Female; hepatic lipase; Humans; Insulin - pharmacology; insulin response element; Lipase - genetics; lipoprotein lipase; Lipoproteins - blood; Male; Middle Aged; Multigene Family; Polymorphism, Genetic; Postprandial Period; remnant-like cholesterol; remnant-like triglyceride; Response Elements; Triglycerides - blood; Czech Republic
• ISSN: 0022-2275
• DOI: 10.1016/s0022-2275(20)32016-2

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 (epsilon2/epsilon3/epsilon4), 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 epsilon2/4 (n = 6) and varepsilon4/4 (n = 3) groups, and thus when the epsilon2/4 group was omitted in order to analyze by allele (epsilon2+/epsilon3+/epsilon4+), significance was lost (P = 0.6). There was strong linkage disequilibrium between the APOE and APOCI alleles (chi(2), 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.