(P10-006-23) Impact of FADS and ELOVL2/5 Genetic Variation on Fatty Acid and Cardiometabolic Endpoints in Mexican American Individuals

Objectives: The largest racial/ethnic minority in the USA, Hispanics, are among those with the highest prevalence of obesity, diabetes, non-alcoholic fatty liver disease, and metabolic syndrome (MetS). Previous studies demonstrate that FADS variants within an ancestral haplotype are associated with a limited capacity to synthesize circulating omega-3 (n-3) highly unsaturated fatty acids (HUFAs). These variants occur in high frequencies in Amerind Ancestry populations, like Mexican Americans (MxAm). This study assesses whether FADS and other variants (ELOVL5 and ELOVL2) in the HUFA biosynthetic pathway impact cardiometabolic disease (CMD) risk in this population.

Methods: Regression models (including covariate adjustments) were used to test for associations between genotypes, fatty acids, and MetS biomarkers in self-identified MxAm participants (N=493). Genotypes evaluated included twenty single nucleotide polymorphisms (SNPs) from the FADS cluster region (chromosome 11) and ELOVL5 and ELOVL2 (both on chromosome 6). The levels of 37 fatty acids (in complex lipids) were assessed by GC/FID detection. Biomarkers for diabetes and MetS included lipoproteins, anthropomorphic markers (weight, height waist-hip ratio), adiponectin, AST/ALT, insulin, glucose and HOMA-IR.

Results: Ancestral FADS genotypes were associated with lower levels of the n-6 HUFA arachidonic acid (ARA), and extremely reduced levels n-3 HUFAs, including eicosapentaenoic acid (EPA) with final ratios of ARA/EPA of ~20:1. Importantly, these same FADS SNPs were strongly associated with MetS phenotypes, including fasting insulin and HOMA-IR factor. FADS SNPs such as rs174455 had substantial effect sizes on fasting insulin and HOMA-IR with each ancestral allele increasing levels by 45% and 41%, respectively.

Conclusions: Robust associations between FADS variants, extremely low n-3 HUFA levels, and CMD biomarkers suggest that regulation of HUFAs levels and ratios may highly impact CMD risk in MxAm populations and provides a strong rationale for a precision nutrition approach utilizing n-3 HUFA supplementation.

Funding Sources: This research was funded by a USDA Project and an NIH grant.