IntroductionPolyunsaturated 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 (FADS) 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.MethodsData 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, aFADShaplotype 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.ResultsThe dietary habits of the cohort showed that participant diets contained a high ratio (9.3 ± 0.2, mean ± SEM) of linoleic acid (n−6) to alpha-linolenic acid (n−3) and also contained extremely low levels ofn−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,n−6) and EPA (20:5,n−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 (p< 0.0001) on the rs174537 genotype (GG > GT > TT) for both circulatingn−6 andn−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 (p= 0.0001) than the GG + GT participants.DiscussionTaken together, this study illustrates that dietary PUFA + HUFA ×FADSgene- interactions place a large proportion (>50%) of Hispanic/Latino populations at high risk of a deficiency in both circulating and cellular levels ofn−3 HUFAs.