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

Waterworth, DM; Hubacek, JA; Pitha, J; Kovar, J; Poledne, R; Humphries, SE; Talmud, PJ; (2000) Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster. J LIPID RES , 41 (7) 1103 - 1109. Gold open access

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 (epsilon 2/epsilon 3/epsilon 4), 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 epsilon 2/4 (n = 6) and epsilon 4/4 (n = 3) groups, and thus when the epsilon 2/4 group was omitted in order to analyze by allele (epsilon 2+/epsilon 3+/epsilon 4+), 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.

Type:Article
Title:Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI-APOE cluster
Open access status:An open access publication
Publisher version:http://www.jlr.org/papbyrecent.shtml
Keywords:insulin response element, remnant-like triglyceride, remnant-like cholesterol, hepatic lipase, lipoprotein lipase, apolipoprotein B, CORONARY-ARTERY DISEASE, EUROPEAN ATHEROSCLEROSIS RESEARCH, RECEPTOR-RELATED PROTEIN, LIPOPROTEIN-LIPASE GENE, APOLIPOPROTEIN-E, COMMON VARIATION, HEART-DISEASE, BETA-VLDL, RISK, POLYMORPHISM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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