FADS1 and FADS2 Gene Polymorphisms Affect Omega-3 and Omega-6 Erythrocyte Fatty Acid Composition and Influence the Association Between Dietary Fatty Acid Intake and Lipid Profile in Brazilian Adults

<b>Background:</b> Polymorphisms in the <i>FADS1</i> and <i>FADS2</i> genes influence fatty acid metabolism. However, evidence of gene-diet interactions in population-based studies from Brazil remains limited. The objective of this study was to examine associations between <i>FADS1-FADS2</i> single-nucleotide polymorphisms (SNPs) and erythrocyte fatty acid composition and serum lipid concentrations, as well as to explore potential gene-diet interactions. <b>Methods</b>: Data were analyzed from 294 adults (20-93 years) enrolled in the 2015 ISA-Nutrition study. Erythrocyte fatty acid composition and serum lipids were measured using standard enzymatic methods. Dietary intake was assessed by 24 h recalls, and participants were classified into tertiles according to fatty acid intake. Five SNPs were genotyped; <i>FADS1</i> rs174546 and <i>FADS2</i> rs174570 were prioritized based on linkage disequilibrium. Associations and interactions were assessed using generalized linear models, adjusting for confounders. <b>Results</b>: Carriers of the minor alleles for rs174546 and rs174570 had significantly lower erythrocyte levels of long-chain polyunsaturated fatty acids, particularly along the ω-6 pathway, suggesting reduced desaturase activity. The rs174546 TT genotype was associated with higher total, very-low-density lipoprotein cholesterol (VLDL), and non-high-density lipoprotein (non-HDL) cholesterolconcentrations. Higher dietary intakes of docosahexaenoic acid (DHA) or a higher linoleic acid to alpha-linolenic acid ratio(LA/ALA ratio) among these carriers were linked to lower serum lipid levels, indicating gene-diet interactions that attenuate adverse genotype effects. In addition, rs174570 TT carriers showed elevated VLDL concentrations, with a significant dietary interaction observed with the LA/ALA ratio. <b>Conclusions</b>: <i>FADS1</i> and <i>FADS2</i> polymorphisms influence fatty acid metabolism and interact with diet to shape lipid profiles. These findings highlight the importance of considering gene-diet interactions in cardiometabolic risk.