Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167, RID-AGE, Facteurs de Risque et Déterminants Moléculaires des Maladies Liées Au Vieillissement, F-59000 Lille, France.
Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167, RID-AGE, Facteurs de Risque et Déterminants Moléculaires des Maladies Liées Au Vieillissement, F-59000 Lille, France.
Clin Nutr. 2018 Oct;37(5):1683-1689. doi: 10.1016/j.clnu.2017.07.012. Epub 2017 Jul 20.
BACKGROUND & AIMS: Blood levels of polyunsaturated fatty acids (PUFAs) are under control of endogenous synthesis via Δ5- and Δ6-desaturases, encoded by the FADS1 and FADS2 genes, respectively and of diet. Genome-wide associations studies (GWAS) reported associations between polymorphisms in FADS1-FADS2 and variations in plasma concentrations of PUFAs, HDL- and LDL-cholesterol and triglycerides. However, it is not established whether dietary PUFAs intake modulates these associations. We assessed whether dietary linoleic acid (LA) or α-linolenic acid (ALA) modulate the association between the FADS1 rs174547 polymorphism (a GWAS hit) and lipid and anthropometric phenotypes.
Dietary intakes of LA and ALA, FADS1 rs174547 genotypes, lipid and anthropometric variables were determined in three French population-based samples (n = 3069). These samples were stratified according to the median dietary LA (<9.5 and ≥9.5 g/d) and ALA (<0.80 and ≥0.80 g/d) intakes. The meta-analysis was performed using a random-effect.
Our meta-analysis confirmed the association between rs174547 and plasma lipid levels and revealed an association with waist circumference and body mass index. These associations were not modified by dietary ALA intake (all p-interaction > 0.05). In contrast, the associations with HDL-cholesterol levels, waist circumference and BMI were modulated by the dietary intake of LA (p interaction < 0.05). In high LA consumers only, the rs174547 minor allele was significantly associated with lower HDL-cholesterol levels (β = -0.05 mmol/L, p = 0.0002). Furthermore, each copy of the rs174547 minor allele was associated with a 1.58 cm lower waist circumference (p = 0.0005) and a 0.46 kg m lower BMI (p = 0.01) in the low LA intake group, but not in the high LA intake group.
The present study suggests that dietary LA intake may modulate the association between the FADS gene variants and HDL-cholesterol concentration, waist circumference and BMI. These gene-nutrient interactions, if confirmed, suggest that subjects carrying the rs174547 minor allele might benefit from low dietary LA intakes.
多不饱和脂肪酸（PUFAs）的血液水平受内源性合成的控制，通过分别由 FADS1 和 FADS2 基因编码的 Δ5-和 Δ6-去饱和酶，以及饮食。全基因组关联研究（GWAS）报道了 FADS1-FADS2 基因多态性与血浆 PUFAs、高密度脂蛋白（HDL）-胆固醇和甘油三酯浓度变化之间的关联。然而，饮食中 PUFAs 的摄入是否调节这些关联尚不清楚。我们评估了饮食中亚油酸（LA）或α-亚麻酸（ALA）是否调节 FADS1 rs174547 多态性（GWAS 命中）与血脂和人体测量表型之间的关联。
在三个法国人群为基础的样本（n=3069）中确定了 LA 和 ALA 的饮食摄入量、FADS1 rs174547 基因型、血脂和人体测量变量。这些样本根据 LA（<9.5 和≥9.5 g/d）和 ALA（<0.80 和≥0.80 g/d）的中位数饮食摄入量进行分层。使用随机效应进行荟萃分析。
我们的荟萃分析证实了 rs174547 与血浆脂质水平之间的关联，并揭示了与腰围和体重指数的关联。这些关联不受饮食 ALA 摄入的影响（所有 p 交互作用>0.05）。相反，LA 饮食摄入量调节了与 HDL-胆固醇水平、腰围和 BMI 的关联（p 交互作用<0.05）。仅在高 LA 消费者中，rs174547 次要等位基因与较低的 HDL-胆固醇水平显著相关（β=-0.05mmol/L，p=0.0002）。此外，在低 LA 摄入组中，每个 rs174547 次要等位基因的拷贝与腰围降低 1.58cm（p=0.0005）和 BMI 降低 0.46kg·m（p=0.01）相关，但在高 LA 摄入组中没有相关性。
本研究表明，饮食 LA 摄入可能调节 FADS 基因变异与 HDL-胆固醇浓度、腰围和 BMI 之间的关联。如果这些基因-营养相互作用得到证实，那么携带 rs174547 次要等位基因的受试者可能受益于低饮食 LA 摄入。
