Sergeant Susan, Keith Brian A, Seeds Michael C, Legins Jimaree A, Young Caroline B, Vitolins Mara Z, Chilton Floyd H
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, United States.
Front Nutr. 2023 May 5;10:1111624. doi: 10.3389/fnut.2023.1111624. eCollection 2023.
Polyunsaturated fatty acids (PUFA) and highly unsaturated fatty acid (HUFA) synthetic products and their signaling metabolites play vital roles in immunity, inflammation, and brain development/function. Frequency differences of variants within the fatty acid desaturase () gene cluster affect levels of HUFAs, their biologically active products, and numerous physiological phenotypes. Fundamental questions remain regarding the impact of this genetic variation on the health of Hispanic/Latino populations.
Data and biospecimens (plasma, red blood cells, buffy coat-derived DNA) from 135 participants (83.7% female) were used to assess the relationship(s) between dietary PUFA levels, a haplotype tagging SNP, rs174537, and the capacity of Hispanic/Latino populations to generate HUFAs in plasma and RBC as well as its potential impact on anthropomorphic phenotypes.
The dietary habits of the cohort showed that participant diets contained a high ratio (9.3 ± 0.2, mean ± SEM) of linoleic acid (-6) to alpha-linolenic acid (-3) and also contained extremely low levels of -3 HUFAs (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA), both features of the Modern Western Diet. Compared to African and European American cohorts, the frequency of the TT rs174537 genotype was highly enriched (53% of subjects) in this Hispanic/Latino cohort and was strongly associated with lower circulating HUFA levels. For example, plasma levels of arachidonic acid (ARA: 20:4, -6) and EPA (20:5, -3) were 37% and 23%, respectively, lower in the TT versus the GG genotype. HUFA biosynthetic efficiency, as determined by metabolic product to precursor ratios, was highly dependent ( < 0.0001) on the rs174537 genotype (GG > GT > TT) for both circulating -6 and -3 HUFAs. In contrast, the RBC Omega-3 Index (EPA + DHA) was extremely low (2.89 ± 1.65, mean ± sd) in this population and independent of rs174537 genotype. Importantly, the rs174537 genotype was also related to female height with TT genotype participants being 4.5 cm shorter ( = 0.0001) than the GG + GT participants.
Taken together, this study illustrates that dietary PUFA + HUFA × gene- interactions place a large proportion (>50%) of Hispanic/Latino populations at high risk of a deficiency in both circulating and cellular levels of -3 HUFAs.
多不饱和脂肪酸（PUFA）和高度不饱和脂肪酸（HUFA）合成产物及其信号代谢物在免疫、炎症和大脑发育/功能中发挥着至关重要的作用。脂肪酸去饱和酶（）基因簇内变体的频率差异会影响高度不饱和脂肪酸、其生物活性产物以及众多生理表型的水平。关于这种基因变异对西班牙裔/拉丁裔人群健康的影响，仍存在一些基本问题。
使用来自135名参与者（83.7%为女性）的数据和生物样本（血浆、红细胞、血沉棕黄层来源的DNA）来评估膳食多不饱和脂肪酸水平、单倍型标签单核苷酸多态性rs174537与西班牙裔/拉丁裔人群在血浆和红细胞中生成高度不饱和脂肪酸的能力之间的关系，以及其对人体形态学表型的潜在影响。
该队列的饮食习惯表明，参与者的饮食中亚油酸（-6）与α-亚麻酸（-3）的比例很高（9.3±0.2，平均值±标准误），并且-3高度不饱和脂肪酸（二十碳五烯酸，EPA和二十二碳六烯酸，DHA）的含量极低，这是现代西方饮食的两个特征。与非洲裔和欧裔美国人队列相比，TT rs174537基因型在该西班牙裔/拉丁裔队列中的频率高度富集（53%的受试者），并且与较低的循环高度不饱和脂肪酸水平密切相关。例如，TT基因型者血浆中花生四烯酸（ARA：20:4，-6）和EPA（20:5，-3）的水平分别比GG基因型者低37%和23%。通过代谢产物与前体的比例确定的高度不饱和脂肪酸生物合成效率，对于循环中的-6和-3高度不饱和脂肪酸，高度依赖于rs174537基因型（GG>GT>TT）（P<0.0001）。相比之下，该人群的红细胞ω-3指数（EPA + DHA）极低（2.89±1.65，平均值±标准差），且与rs174537基因型无关。重要的是，rs174537基因型还与女性身高有关，TT基因型参与者比GG + GT参与者矮4.5厘米（P = 0.0001）。
综上所述本研究表明，膳食多不饱和脂肪酸+高度不饱和脂肪酸×基因相互作用使很大一部分（>50%）西班牙裔/拉丁裔人群面临循环和细胞水平的-3高度不饱和脂肪酸缺乏的高风险。
