1. Amerind ancestry predicts the impact of FADS genetic variation on omega-3 PUFA deficiency, cardiometabolic and inflammatory risk in Hispanic populations
- Author
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Jin Choul Chai, Lawrence J. Mandarino, Ingo Ruczinski, Dawn K. Coletta, Floyd H. Chilton, Alexis C. Wood, Lyn M. Steffen, Robert C. Kaplan, Qibin Qi, Rozenn N. Lemaitre, Sarah A. Blomquist, Brian Hallmark, Michael Y. Tsai, Chaojie Yang, Laurel Johnstone, Michael C. Seeds, Y. D.I. Chen, Martha L. Daviglus, Lindsay M. Reynolds, Ani Manichaikul, Amanda M. Fretts, Timothy D. O’Connor, Stephen S. Rich, Chandra Tontsch, and R. Mathias more...
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Genetics ,Insulin resistance ,Genetic genealogy ,Diabetes mellitus ,Genetic variation ,medicine ,SNP ,lipids (amino acids, peptides, and proteins) ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,Obesity ,Dyslipidemia - Abstract
Hispanic populations have higher rates of obesity, elevated triglycerides, and a greater prevalence of diabetes. Long chain polyunsaturated fatty acids (LC-PUFAs) and LC-PUFA metabolites have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS cluster accounts for a large part of the 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 (AI) ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation, plasma phospholipid levels of LC-PUFAs, anthropometric measures, and circulating metabolic and inflammatory biomarkers in 1,102 Hispanic American participants, representing six distinct ancestry populations from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between AI 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. We further replicated the association with circulating TGs in two additional Hispanic cohorts: the Hispanic Community Health Study/Study of Latinos and the Arizona Insulin Resistance Registry. 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. more...
- Published
- 2021
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