Chilton Floyd H, Manichaikul Ani, Yang Chaojie, O'Connor Timothy D, Johnstone Laurel M, Blomquist Sarah, Schembre Susan M, Sergeant Susan, Zec Manja, Tsai Michael Y, Rich Stephen S, Bridgewater Susan J, Mathias Rasika A, Hallmark Brian
School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States.
BIO5 Institute, University of Arizona, Tucson, AZ, United States.
Front Nutr. 2022 Feb 8;8:808054. doi: 10.3389/fnut.2021.808054. eCollection 2021.
Human diets in developed countries such as the US have changed dramatically over the past 75 years, leading to increased obesity, inflammation, and cardiometabolic dysfunction. Evidence over the past decade indicates that the interaction of genetic variation with changes in the intake of 18-carbon essential dietary omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), respectively, has impacted numerous molecular and clinical phenotypes. Interactions are particularly relevant with the and genes, which encode key fatty acid desaturases in the pathway that converts LA and ALA to their long chain (≥20 carbons), highly unsaturated fatty acid (HUFA) counterparts. These gene by nutrient interactions affect the levels and balance of n-6 and n-3 HUFA that in turn are converted to a wide array of lipids with signaling roles, including eicosanoids, docosanoids, other oxylipins and endocannabinoids. With few exceptions, n-6 HUFA are precursors of pro-inflammatory/pro-thrombotic signaling lipids, and n-3 HUFA are generally anti-inflammatory/anti-thrombotic. We and others have demonstrated that African ancestry populations have much higher frequencies (vs. European-, Asian- or indigenous Americas-ancestry populations) of a "derived" haplotype that is associated with the efficient conversion of high levels of dietary n-6 PUFA to pro-inflammatory n-6 HUFA. By contrast, an "ancestral" haplotype, carrying alleles associated with a limited capacity to synthesize HUFA, which can lead to n-3 HUFA deficiency, is found at high frequency in certain Hispanic populations and is nearly fixed in several indigenous populations from the Americas. Based on these observations, a focused secondary subgroup analysis of the VITAL n-3 HUFA supplementation trial stratifying the data based on self-reported ancestry revealed that African Americans may benefit from n-3 HUFA supplementation, and both ancestry and variability should be factored into future clinical trials design.
在过去75年里，美国等发达国家的人类饮食发生了巨大变化，导致肥胖、炎症和心血管代谢功能障碍增加。过去十年的证据表明，遗传变异与18碳必需膳食ω-6（n-6）和ω-3（n-3）多不饱和脂肪酸（PUFA）（分别为亚油酸（LA）和α-亚麻酸（ALA））摄入量变化之间的相互作用，影响了众多分子和临床表型。这些相互作用与 和 基因尤其相关，这两个基因在将LA和ALA转化为其长链（≥20个碳）、高度不饱和脂肪酸（HUFA）对应物的途径中编码关键脂肪酸去饱和酶。这些基因与营养素的相互作用会影响n-6和n-3 HUFA的水平和平衡，进而转化为具有信号传导作用的多种脂质，包括类二十烷酸、二十二碳六烯酸、其他氧化脂质和内源性大麻素。除了少数例外，n-6 HUFA是促炎/促血栓形成信号脂质的前体，而n-3 HUFA通常具有抗炎/抗血栓形成作用。我们和其他人已经证明，非洲裔人群中一种“衍生”单倍型的频率要高得多（与欧洲、亚洲或美洲原住民血统人群相比），这种单倍型与将高水平膳食n-6 PUFA有效转化为促炎性n-6 HUFA有关。相比之下，一种“祖先”单倍型在某些西班牙裔人群中高频出现，在美洲的几个原住民群体中几乎固定存在，该单倍型携带的等位基因与合成HUFA的能力有限有关，这可能导致n-3 HUFA缺乏。基于这些观察结果，对VITAL n-3 HUFA补充试验进行的一项重点二级亚组分析，根据自我报告的血统对数据进行分层，结果显示非裔美国人可能从n-3 HUFA补充中受益，血统和 变异性都应纳入未来临床试验设计中。
