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dc.contributor.authorChilton, Floyd H
dc.contributor.authorManichaikul, Ani
dc.contributor.authorYang, Chaojie
dc.contributor.authorO'Connor, Timothy D
dc.contributor.authorJohnstone, Laurel M
dc.contributor.authorBlomquist, Sarah
dc.contributor.authorSchembre, Susan M
dc.contributor.authorSergeant, Susan
dc.contributor.authorZec, Manja
dc.contributor.authorTsai, Michael Y
dc.contributor.authorRich, Stephen S
dc.contributor.authorBridgewater, Susan J
dc.contributor.authorMathias, Rasika A
dc.contributor.authorHallmark, Brian
dc.date.accessioned2022-03-02T14:26:27Z
dc.date.available2022-03-02T14:26:27Z
dc.date.issued2022-02-08
dc.identifier.urihttp://hdl.handle.net/10713/18136
dc.description.abstractHuman 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 FADS1 and FADS2 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 FADS "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 FADS variability should be factored into future clinical trials design.en_US
dc.description.urihttps://doi.org/10.3389/fnut.2021.808054en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Nutritionen_US
dc.rightsCopyright © 2022 Chilton, Manichaikul, Yang, O'Connor, Johnstone, Blomquist, Schembre, Sergeant, Zec, Tsai, Rich, Bridgewater, Mathias and Hallmark.en_US
dc.subjectancestryen_US
dc.subjectendocannabinoiden_US
dc.subjectfatty acid desaturaseen_US
dc.subjectgene-diet interactionen_US
dc.subjectomega-3 deficiency syndromeen_US
dc.subjectomega-3 supplementsen_US
dc.subjectoxylipinsen_US
dc.subjectpolyunsaturated fatty aciden_US
dc.titleInterpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and Genetic Variation.en_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fnut.2021.808054
dc.identifier.pmid35211495
dc.source.journaltitleFrontiers in nutrition
dc.source.volume8
dc.source.beginpage808054
dc.source.endpage
dc.source.countrySwitzerland


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