Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations

Chaojie Yang,Alexis C Wood,Timothy D O’Connor,Michael C Seeds ,Laurel Johnstone ,Stephen S Rich,Michael Y Tsai,Lyn M Steffen,Dawn K Coletta,Ingo Ruczinski,Yii Der Ida Chen ,Rasika A Mathias,Chandra Tontsch,Jin Choul Chai,Rozenn N Lemaître ,Robert C Kaplan,Lawrence J Mandarino,Sarah Blomquist ,Lindsay M Reynolds,Amanda M Fretts,Martha L Daviglus,Qibin Qi,Brian Hallmark,Floyd H Chilton,Ani Manichaikul

doi:10.1038/s42003-021-02431-4

Abstract

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

Highlights

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation
Between subjects with the lowest and highest proportions of AI ancestry, the n-3 LCPUFAs decreased by 60.6% and 46.8% and the n-6 LC-PUFAs decreased by 30.7%
In light of dramatic differences in genetic variation within the fatty acid desaturase (FADS) locus across worldwide populations[56] and the marked changes in dietary n-6 and n-3 PUFA levels and ratios over the past 75 years, we carried out a study of to examine genomic proportion of AI ancestry as a predictor of n-3 and n-6 LC-PUFA levels and related cardiometabolic and inflammatory risk in the Hispanic participants from Multi-Ethnic Study of Atherosclerosis (MESA)

Summary

Introduction

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Hispanics identifying with the higher Amerind (AI)-ancestry origin have demonstrated enhanced urine albumin excretion[9], heart failure[10], lupus erythematosus risk[11], and prevalence of NAFLD compared to other Hispanic populations[12], supporting the critical need to conduct studies in these large, rapidly growing populations. Early studies with deuterated substrates indicated there is a saturation point where additional dietary quantities of 18 carbon dietary substrates had no effect on circulating LC-PUFA levels[37] These studies estimated that conversion of dietary ALA provided 75–85% of total n-3 LC-PUFAs needed to meet daily requirements[37]

Methods

Results

Conclusion