Genetic Variants in the FADS Gene: Implications for Dietary Recommendations for Fatty Acid Intake

Abstract

Unequivocally, genetic variants within the fatty acid desaturase (FADS) cluster are determinants of long chain polyunsaturated fatty acid (LC-PUFA) levels in circulation, cells and tissues. A recent series of papers have addressed these associations in the context of ancestry; evidence clearly supports that the associations are robust to ethnicity. However ∼80% of African Americans carry two copies of the alleles associated with increased levels of arachidonic acid, compared to only ∼45% of European Americans raising important questions of whether gene-PUFA interactions induced by a modern western diet are differentially driving the risk of diseases of inflammation in diverse populations, and are these interactions leading to health disparities. We highlight an important aspect thus far missing in the debate regarding dietary recommendations; we content that current evidence from genetics strongly suggest that an individual's, or at the very least the population from which an individual is sampled, genetic architecture must be factored into dietary recommendations currently in place.

Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes

“…However, mounting evidence indicates that common genetic and epigenetic variations in close proximity to and within the FADS cluster markedly affect the rate of conversion of 18C-PUFAs, including GLA, to LC-PUFAs and thus affecting the amount of circulating and tissue LC-PUFA levels. Specifically, single nucleotide polymorphisms (SNPs) and the methylation status of CpG sites in the FADS gene cluster are strongly associated with DGLA, AA and DHA levels in plasma and liver tissues (Chilton et al, 2014; Hoile et al, 2014; Howard et al, 2014; Mathias et al, 2014). As discussed in section 2, the human FADS gene cluster is located on chromosome 11q12-q13.1, comprised of 91.9kb and has nearly 500 SNPs annotated to this region with exon/intron organization (Fig.…”

The impact of fatty acid desaturase genotype on fatty acid status and cardiovascular health in adults

“…A potential reason for these findings could involve the high LA intakes in the Western diet, resulting in reduced synthesis of LC n-3 PUFA from αLNA (32) . The higher n-6 conversion also leads to increased levels of AA, which is a direct precursor of many pro-inflammatory eicosanoids (33,34) . Hester et al (33) recently showed that subjects with the major allele for FADS SNP rs174537 had significantly higher levels of pro-inflammatory eicosanoids, LTB4 and 5-HETE, compared with minor allele carriers (33) .…”

Global Estimates of Dietary Intake of Docosahexaenoic Acid and Arachidonic Acid in Developing and Developed Countries

“…As a consequence, the balance in the intake of the essential 18-carbon n-3 and n-6 precursors can influence the levels of DHA and ARA derived from endogenous synthesis [7]. Moreover, it is now recognised that this metabolic pathway is relatively inefficient in converting n-3 and n-6 precursor fatty acids to DHA and ARA respectively, especially in early life when organ development is at its peak [8,9,10,11,12,13].…”

“…It is now recognised that, in addition to substrate competition, the efficiency of the Δ5- and Δ6-desaturase steps is also dependent on the genotype of fatty acid desaturase (FADS) 1 and FADS2, both located on chromosome 11, and which encode Δ5- and Δ6-desaturase enzymes, respectively [7]. Several studies have reported associations between single nucleotide polymorphisms (SNPs) in the FADS genes and LCPUFA status, with carriers of the minor alleles of FADS SNPs being associated with lower red blood cell content of LCPUFAs, most notably of ARA [14,15].…”