在一项随机临床试验中，单核苷酸多态性的组合与个体对饮食脂肪酸摄入的血脂反应的个体间变异性有关。

A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial.

机构信息

Richardson Centre for Functional Foods and Nutraceuticals (RCFFN), Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

École de nutrition, Université Laval, Laval, Quebec, Canada.

出版信息

Am J Clin Nutr. 2021 Aug 2;114(2):564-577. doi: 10.1093/ajcn/nqab064.

DOI:10.1093/ajcn/nqab064

PMID:33871574

Abstract

BACKGROUND

Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes.

OBJECTIVE

We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions.

DESIGN

In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression.

RESULTS

Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA: 3.00 ± 0.04, PUFA: 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P < 0.001) while endpoint TG concentrations were not (P = 0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5 ± 2.2% and 55.8 ± 1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes.

CONCLUSIONS

We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.

摘要

背景

血脂浓度在对饮食干预的反应中表现出高度的个体间变异性，部分原因是遗传因素。现有研究主要集中在单个核苷酸多态性（SNP）的分析上，这些分析只能解释这些复杂表型变异性的有限部分。

目的

我们旨在确定与 LDL 胆固醇和甘油三酯（TG）浓度变化相关的 SNP 组合，这些变化是在 5 种饮食干预后的结果。

设计

在一项多中心随机交叉试验中，92 名腰围升高且 HDL 胆固醇浓度较低的参与者摄入了 5 种等热量饮食，持续 4 周：一种富含奶酪饱和脂肪酸（SFA）的饮食、一种富含黄油 SFA 的饮食、一种富含单不饱和脂肪酸（MUFA）的饮食、一种富含 n-6 多不饱和脂肪酸（PUFA）的饮食和一种富含碳水化合物（CHO）的饮食。采用单变量统计分析和偏最小二乘回归评估了涉及脂质和胆汁酸代谢和转运的 22 个候选基因中的 SNP 与 LDL 胆固醇和 TG 浓度变化之间的关联。

结果

终点 LDL 胆固醇浓度差异显著（奶酪：3.18±0.04mmol/L，黄油：3.31±0.04mmol/L，MUFA：3.00±0.04mmol/L，PUFA：2.81±0.04mmol/L，CHO：3.11±0.04mmol/L；P＜0.001），而终点 TG 浓度没有差异（P=0.117）。两种方法均显示出饮食干预后个体间变异性持续升高（分别为 34.5±2.2%和 55.8±1.8%）。在 22 个候选 SNP 中，只有 ABCA1-rs2066714 和载脂蛋白 E（APOE）异构体表现出一致的显著影响，即对 LDL 胆固醇浓度的影响。然而，一些 SNP 与 LDL 胆固醇和 TG 浓度的变化在特定的饮食方式下显著相关。生成的多元模型解释了 LDL 胆固醇浓度变化的个体间变异性的 16.0%至 33.6%，以及 TG 浓度变化的 17.5%至 32.0%。