FADS2 Variants are Associated with Omega-6 Metabolic Conversion in Serbian Adults in a cross-sectional study – Implications for Precision Nutrition Practice

Background High omega-6/omega-3 intake ratio in westernized world is of concern. FADS genes variants are associated with plasma long-chain polyunsaturated fatty acids (LC-PUFA) in diverse ethnicities and might modulate plasma omega-6/omega-3 net balance. Therefore, the objective of this study was to evaluate the relationships between FADS genetic variants with dietary fat and macronutrient intake, plasma phospholipid fatty acid profile, estimated plasma desaturase activity and cardiometabolic risk factors, in a sample of Serbian subjects.Methods Non-smoking adult volunteers (>28 years), free of acute or chronic disease were included. Food and nutrient data were compiled through 24h recalls for non-consecutive days. Plasma phospholipid fatty acid content was assessed by gas-chromatography. Selection of FADS2 variants (rs174593, rs174616 and rs174576) was based on its positional and functional aspect, and evidence-based data. Genotyping was performed by using Real-Time PCR. Estimated desaturase activities were calculated as conversion rates towards LC-PUFA in omega-6 pathway. Multivariable-adjusted general linear were applied and the contribution of minor alleles to the variability of physiological parameters was analyzed by multivariable hierarchical multiple regression models.Results Sample included 34 men and 54 women, mean age=40±7years, with 70% being overweight (BMI>25). Minor allele frequencies were 33%, 36% and 51% for rs174593, rs174576 and rs174616, respectively, in line with other populations. None of the three variants was associated with food or nutrient intake, serum lipids, or obesity (p>0.05). Irrespective of gender, age, total daily polyunsaturated/saturated fatty acid intake and obesity, rs174593, rs174616 and rs174576 were associated with lower arachidonic acid (AA, C20:4 n-6, p<0.001) and estimated desaturase-5 activity (p<0.001) in plasma phospholipids. The rs174576 associations with AA withstood multiple testing and additional adjustments for other variants.Conclusion We observed inverse associations between FADS2 variants and plasma phospholipid AA but not omega-3 fatty acids in a sample of Serbian adults, and larger cohorts should confirm the associations. In our study FADS2 rs174576 exhibited the strongest associations, and future gene-dietary studies with varying omega-6/omega-3 intake should validate its suitability for precision nutrition strategies aimed at PUFA recommendations in Serbian population.Trial registration This is a cross-sectional study, forming part of larger intervention study registered at ClinicalTrials.gov as NCT02800967.