Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and γ-linolenic acid-containing botanical oils
Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and γ-linolenic acid-containing botanical oils
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DOI：
10.1093/ajcn/nqaa023
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发表时间：
2020-05-01
影响因子：
7.1
通讯作者：
Chilton, Floyd H.
中科院分区：
文献类型：
--
作者：
Sergeant, Susan;Hallmark, Brian;Chilton, Floyd H.
背景资料：临床试验中无法解释的异质性导致了关于含有γ-亚麻酸（GLA）的植物油补充剂有效性的问题。这种异质性可以通过脂肪酸去饱和酶（FADS）基因簇内的遗传变异来解释，该基因簇与花生四烯酸（ARA）和二高-γ-亚麻酸（DGLA）的循环和组织浓度相关，这两者都可以从GLA合成并分别产生促炎和抗炎代谢产物。目的：本研究的目的是前瞻性比较非西班牙裔白色队列的能力，根据关键单核苷酸多态性（SNP）rs 174537的FADS基因型分层，将琉璃苣油（BO）和大豆油（SO）中的18碳ω-6（n-6）PUFA代谢为GLA、DGLA。方法：健康成人（n = 64）参加了一个随机，双盲，交叉干预。个体接受包封的BO（Borago officinalis L.; 37%LA和23%GLA）或SO [Glycine max（L.）男人。50%LA和0%GLA] 4周，然后是8周的洗脱期，然后食用相反的油4周。血脂和炎症标志物（C-反应蛋白）进行了评估，这两种油类型在基线和第2周和第4周的intervention.Results：SO补充未能改变任何n-6长链PUFA的循环浓度。相比之下，中等日剂量的BO以rs 174537基因型依赖性方式升高GLA和DGLA的血清浓度。特别地，GG基因型个体中DGLA增加了57%（95%CI：0.38，0.79），但GG基因型个体中DGLA增加了141%（95%CI：1.03）。2.85）在TIT个体中。对于ARA，基线浓度变化很大的基因型和增加适度BO补充剂，这表明FADS的变化在DGLA和ARA.Conclusions平衡的关键作用：本研究的结果清楚地表明，个性化和基于人群的方法考虑FADS遗传变异可能是必要的，以优化设计未来的临床研究与含GLA的油。
Background: Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of gamma-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-gamma-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively.Objectives: The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleoside polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA. and ARA.Methods: Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Men.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention.Results: SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03. 2.85) in TiT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA.Conclusions: The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils.