APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome

Rosalind Fallaize,Rosalind Fallaize,Andrew L Carvalho-Wells,Ulf Risérus,Beata Kieć-Wilk,Wim H Saris,Julie A Lovegrove,Helen M Roche,Christian A Drevon,Carmen Marin,Ellen E Blaak,Catherine Defoort,Aldona Dembińska-Kieć,Audrey C Tierney,José Lopez-Miranda

doi:10.1038/s41598-017-05802-2

Abstract

Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.

Highlights

The Metabolic Syndrome (MetS) is characterized by a clustering of risk factors related to cardiovascular disease (CVD) and type-II diabetes (T2D), including abdominal obesity, insulin resistance, hypertension, dyslipidemia and inflammation[1, 2]
A geographic cline can be seen with respect to allele frequency, with the most southerly country expressing the lowest frequency of the ε4 allele and the most northerly country greater than 2-fold higher (E3/E4 and E4/E4 combined frequency, 8.6% for Cordoba, Spain versus 22.8% for Oslo, Norway)
A beneficial impact of increasing plasma LC n-3 polyunsaturated FA (PUFA) on apo CII concentrations in E2 carriers, and a detrimental association between high plasma saturated fatty acids (SFA) and insulin resistance in E4 carriers at baseline was observed. This is the first study to examine the impact of change in plasma FA, from dietary fat intervention, on lipids and insulin resistance in a MetS population

Summary

Introduction

The Metabolic Syndrome (MetS) is characterized by a clustering of risk factors related to cardiovascular disease (CVD) and type-II diabetes (T2D), including abdominal obesity, insulin resistance, hypertension, dyslipidemia and inflammation[1, 2]. The primary goal of clinical management is to reduce risk for metabolic and atherosclerotic disease[4] This is achieved by targeting modifiable risk factors such as obesity, physical inactivity and inappropriate diets, in addition to smoking. Unhealthy diets, such as those high in saturated fatty acids (SFA), have been shown to increase low-density lipoprotein cholesterol (LDL-C) and CVD risk[5]. The ε4 allele has been associated with increased TC, LDL-C, coronary artery disease (CAD) mortality and reduced high-density lipoprotein cholesterol (HDL-C) concentrations[12, 15,16,17,18,19]. We examined the relationship between the missense APOE polymorphism, habitual FA status and following dietary FA intervention on metabolic markers in a MetS population

Methods

Results

Conclusion