1.
Disrupted fatty acid distribution in HDL and LDL according to apolipoprotein E allele.
Dang, TM, Conway, V, Plourde, M
Nutrition (Burbank, Los Angeles County, Calif.). 2015;(6):807-12
Abstract
OBJECTIVES Omega-3 polyunsaturated fatty acid (ω-3 PUFA) metabolism seems to be disrupted in carriers of the epsilon 4 allele of apolipoprotein E (E4+). The objective of this study was to investigate whether the ω-3 PUFA distribution in the high and low density lipoproteins is APOE-genotype dependant before and after supplementation with ω-3 PUFAs. METHODS Eighty participants, aged between 20 and 35 y old were recruited and supplemented with 900 mg of eicosapentaenoic acid plus 680 mg of docosahexaenoic acid for 4 wk. Over the 4-wk intervention, blood samples were collected and HDL and LDL particles were obtained using sucrose gradient ultracentifugation. Fatty acid profiles of the HDL and LDL fractions were performed by gas chromatography. RESULTS Baseline anthropometric characteristics of participants were not significantly different between the two APOE-groups (E4+, N = 10; E4-, N = 70). At baseline, in the LDL of E4+ subjects, the ω-6/ω-3 PUFA ratio was 17% higher than E4- subjects. At week 4, the ω-6/ω-3 PUFA ratio was significantly higher in the LDL of E4+ than E4- subjects. There was a significant genotype × time interaction for 16:0 in HDL and LDL and for 18:2 ω-6 in HDL. DHA in the HDL was positively correlated to HDL-C levels pre- and postsupplementation in E4- only. CONCLUSIONS Contrary to what we anticipated, ω-3 PUFAs content? in HDL and LDL were not APOE isoform-dependant in young participants. However, young E4+ participants already had a tendency toward lower baseline-DHA levels in LDL particles as well as a more atherogenic ω-6/ω-3 PUFA ratio in LDL pre- and post-supplementation.
2.
Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers.
Majewicz, J, Rimbach, G, Proteggente, AR, Lodge, JK, Kraemer, K, Minihane, AM
Biochemical and biophysical research communications. 2005;(2):951-5
Abstract
The deleterious impact of cigarette smoking on cardiovascular health may be in part attributable to a free radical mediated proinflammatory response in circulating monocytes. In the current investigation, the impact of vitamin C supplementation on monocyte gene expression was determined in apoE4 smokers versus non-smokers. A total of 10 smokers and 11 non-smokers consumed 60mg/day of vitamin C for four weeks and a fasting blood sample was taken at baseline and post-intervention for the determination of plasma vitamin C and monocyte gene expression profiles using cDNA array and real time PCR. In apoE4 smokers, supplementation resulted in a 43% increase in plasma vitamin C concentrations. Furthermore, a number of genes were differentially expressed more than 2-fold in response to treatment, including a downregulation of the proinflammatory mediators tumor necrosis factor (TNF) beta, TNF receptor, neurotrophin-3 growth factor receptor, and monocyte chemoattractant protein 1 receptor. The study has identified a number of molecular mechanisms underlying the benefit of vitamin C supplementation in smokers.
3.
Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.
Ballantyne, CM, Herd, JA, Stein, EA, Ferlic, LL, Dunn, JK, Gotto, AM, Marian, AJ
Journal of the American College of Cardiology. 2000;(5):1572-8
Abstract
OBJECTIVES We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown. METHODS Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment. RESULTS Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events. CONCLUSIONS Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.