FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain

Thais S Rizzi,Peter Heutink,Matthijs Verhage,Sophie Van Der Sluis,Robert Vlietinck,Ronald E Van Kesteren,Nele Jacobs,Evert Thiery,Catherine Derom,Danielle Posthuma,Sofie Van Gestel

doi:10.1371/journal.pone.0068000

Abstract

Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition.

Highlights

Dietary fatty acids are increasingly recognized to have important effects on health outcomes and diseases
We used publicly available genotypic and brain expression data of human donors [33] and mouse data [34]. In this second study we investigated whether genetic variants in the FA desaturase (FADS) cluster region affect FADS1, FADS2 and FADS3 brain expression
In addition we investigated whether FADS2 genotype is related to the exposure to breast feeding (BF), and whether FADS2 genotype is related to gestational age and birth weight

Summary

Introduction

Dietary fatty acids are increasingly recognized to have important effects on health outcomes and diseases. Fatty acids affect a number of physiological processes in their role as energy substrates, structural and functional components of cell membranes, precursors of lipid mediators, and components affecting signal transduction pathways and gene transcription [1,8,9,10,11]. These and other effects of fatty acids are suggested to be mediated to a large extent by the availability of the long-chain poly unsaturated fatty acids (LC-PUFA), including arachidonic acid [ARA; 20:4(n-6)], docosahexaenoic acid [DHA; 22:6(n-3)] and eicosapentaenoic acid [EPA; 20:5(n-3)] [5]. In the absence of oily sea fish consumption, intakes of DHA are very low [14,15]

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