ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype

Abstract

Abstract-The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m 2 , triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] Ͻ1.1 mmol/l, and percent low density lipoprotein [LDL]-3 Ͼ40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% (PϽ0.001), in postprandial TG response of 26% (TG area under the curve, PϽ0.001), and in percent LDL-3 of 26% (PϽ0.05). However, no change in HDL-C levels was evident (Pϭ0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers (Pϭ0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, Pϭ0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.

Effects of marine n-3 fatty acid supplementation on lipoprotein subclasses measured by nuclear magnetic resonance in subjects with type II diabetes

“…This finding is contrary to the reducing effect on small, dense LDL by marine n-3 FA reported in subjects with hypertriglyceridemia (Baumstark et al, 1992;Minihane et al, 2000;Wilkinson et al, 2005). The presence or absence of hypertriglyceridemia could be an important factor for the effect of n-3 FA on small LDL as could the large intake of fish oil in our study, which resembles the one given to healthy subjects in which an increase in LDL apolipoprotein B was reported (Sullivan et al, 1986).…”

Methodology for studying postprandial lipid metabolism

“…In that case, a similar standardized test meal is to be used in every subject. (Weintraub et al, 1988(Weintraub et al, , 1989Lopez-Miranda et al, 1997Patsch et al, 1992;Mekki et al, 1999;Minihane et al, 2000;Tiret et al, 2000;Sharrett et al, 2001;Robertson et al, 2002;Jackson et al, 2003;Harbis et al, 2004).…”

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

“…Recent evidence (Minihane et al 2000) also suggests that apoE genotype may in part predict the LDLC response to fish oil fatty acid intervention. The variability of LDLCraising effect of EPA and DHA has been frequently reported (Harris, 1997).…”

“…The variability of LDLCraising effect of EPA and DHA has been frequently reported (Harris, 1997). In a study of individuals with an atherogenic lipoprotein phenotype (Minihane et al 2000) retrospective genotyping suggests that the LDLC-raising effects observed following supplementation with 3 g EPA + DHA/d are associated with an apoE4 genotype. Additional studies are currently underway to investigate EPA/DHA-LDLC associations.…”