Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health

Abstract

Blood and tissue contents of polyunsaturated fatty acid (PUFA) and long-chain PUFA (LC-PUFA) are related to numerous health outcomes including cardiovascular health, allergies, mental health and cognitive development. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA and LC-PUFA status. Recent results suggest that in addition to fatty acid desaturase 1 and fatty acid desaturase 2, the gene product of fatty acid desaturase 3 is associated with desaturating activity. New data have become available to show that FADS single nucleotide polymorphisms (SNPs) also modulate docosahexaenoic acid status in pregnancy as well as LC-PUFA levels in children and in human milk. There are indications that FADS SNPs modulate the risk for allergic disorders and eczema, and the effect of breastfeeding on later cognitive development. Mechanisms by which FADS SNPs modulate PUFA levels in blood, breast milk and tissues should be explored further. More studies are required to explore the effects of FADS gene variants in populations with different ethnic backgrounds, lifestyles and dietary habits, and to investigate in greater depth the interaction of gene variants, diet and clinical end points, including immune response and developmental outcomes. Analyses of FADS gene variants should be included into all sizeable cohort and intervention studies addressing biological effects of PUFA and LC-PUFA in order to consider these important confounders, and to enhance study sensitivity and precision.

Figure 1

The omega‐9, omega‐6, and omega‐3 fatty acid metabolism pathways. FADS1, fatty acid desaturase 1; FADS2, fatty acid desaturase 2; SCD, stearoyl‐CoA desaturase; D5D, delta‐5 desaturase; D6D, delta‐6 desaturase; D8D, delta‐8 desaturase; D9D, delta‐9 desaturase.

Figure 2

The human FADS gene cluster located on chromosome 11 with exon/intron organization and location of some published SNPs shown to be associated with fatty acid and phospholipid levels. SNP rs174537 is located 13.7 kb upstream of FADS1 (//indicates change of scaling). FADS, fatty acid desaturase; SNPs, single nucleotide polymorphisms; FADS1, fatty acid desaturase 1; FADS2, fatty acid desaturase 2; FADS3, fatty acid desaturase 3.