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• W3010373125 abstract "Hispanic populations in the US have increased risk of obesity, elevated circulating triglycerides, nonalcoholic fatty liver disease, and diabetes. Our previous studies suggest that ancestry-related differences in the frequency of variants in the fatty acid desaturase ( FADS) gene cluster in the context of the modern Western diet can lead to inadequate circulating and tissues levels of n-3 long-chain (LC-; ≥ 20 carbons) polyunsaturated fatty acids (PUFA); these deficiencies in turn have the capacity to increase metabolic disease risk. Specifically, we and others have demonstrated Amerindian (AI)-Ancestry populations have high frequencies of FADS gene variants that may lead to less efficient n-3 LC-PUFA biosynthesis. To test this hypothesis, concentrations of fatty acids, including LC-PUFAs in plasma phospholipids were analyzed in 1,102 Hispanic American participants from Multi-Ethnic Study of Atherosclerosis (MESA) cohort, which represent six Hispanic subgroups based on self-reported region of origin: Central America, South America, Mexico, Cuba, Dominican Republic, and Puerto Rico. These data revealed a striking inverse relationship between genome-wide AI-ancestry and levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Additional analyses revealed that the genotype at FADS SNP rs174537, for which the frequency of the T allele increases with AI-ancestry, could primarily explain the associations. There also was a strong association between the number of T alleles (additive model) at rs174537 and circulating triglycerides (18.5 mg/dL per T allele; P =2.0 x 10 -5 ) as well as an important marker of vascular inflammation sICAM-1 (β=12.7 ng/mL, P =0.02). We also genotyped the FADS SNP, rs174537, in a separate adult Arizona Hispanic cohort (Arizona Insulin Resistance [AIR] registry) and compared the FADS genotypic frequencies with other racial/ethnic groups. Importantly, the TT genotype associated with limited LC-PUFA biosynthesis ranges from <1% in African-Ancestry populations to 40.2% in AI-Ancestry Hispanics in the AIR Registry, with ~11 % in European-Ancestry populations. These data demonstrate that high AI-ancestry populations have a dramatically higher frequency of the TT genotype versus African and European populations. Importantly similar to MESA, there also was a significant association between the number of T alleles and plasma triglycerides (p = 0.0036; GG = 125±8.18 mg/dl, GT = 135±5.63 mg/dl, TT = 143±5.58 mg/dl) again suggesting the AI-associated TT genotype places this population at higher risk of hypertriglyceridemia. Together, these data reveal that FADS gene*dietary PUFA interactions give rise to n-3 LC-PUFA deficiencies and may enhance metabolic and inflammatory diseases in a large proportion of individuals in AI-Ancestry Hispanic populations." @default.
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• W3010373125 date "2020-03-03" @default.
• W3010373125 modified "2023-10-05" @default.
• W3010373125 title "Abstract MP67: Fatty Acid Desaturase Gene-induced Omega-3 Deficiency In Amerindian-Ancestry Hispanic Populations" @default.
• W3010373125 doi "https://doi.org/10.1161/circ.141.suppl_1.mp67" @default.
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