Prostaglandins Leukot Essent Fatty Acids., 2019., Sep 13;150:38-46. doi: 10.1016/j.plefa.2019.09.004.

Maternal polymorphisms in the FADS1 and FADS2 genes modify the association between PUFA ingestion and plasma concentrations of omega-3 polyunsaturated fatty acids.

Carvalho GQ Pereira-Santos M Marcon LD et al.

Abstract

There is a lack of studies about polymorphisms in FADS genes in pregnant women. We aimed to verify the interaction between three FADS gene polymorphisms (rs174561; rs174575; rs3834458) and dietary α-linolenic acid (ALA) or linoleic/α-linolenic acid ratio (LA/ALA) and plasma concentrations of omega-3 (n-3) PUFAs in pregnant women. Of the 250 women evaluated, the homozygous for the rs174561 and rs3834458 minor allele had high plasma ALA concentrations at the highest ALA and LA/ALA ratio tertile (p < 0.05). Plasma concentrations of EPA and DHA were not influenced by diet. For the rs174575 SNP, pregnant women who carried the minor allele presented lower proportions of plasma EPA in the second LA/ALA ratio tertile (p < 0.05). Increased dietary intake of ALA and LA/ALA ratio promoted plasma ALA accumulation in homozygotes for the minor allele rs174561 and rs3834458. Moderate intake of LA/ALA ratio may reduce plasma concentration of EPA in pregnants carrying the rs174575 minor allele.

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Key Points

Due to the genetic regulation of enzyme steps, the existence of single nucleotide polymorphisms (SNPs) in FADS genes has been associated with changes in blood concentrations of polyunsaturated fatty acids (PUFAs).  Studies also show controversial results, because only some SNPs can reduce LCPUFA concentrations, but in certain studies the same loci may have no effects or the results are contradictory.

Considering that gene-nutrient interactions influence the plasma concentrations of long-chain polyunsaturated fatty acids and their ALA and LA precursors, this study aimed to verify if FADS1 (rs174561) and FADS2 (rs174575 and rs3834458) polymorphisms affect the relationship between dietary α-linolenic acid (ALA) or LA/ALA ratio and plasma concentrations of omega-3 polyunsaturated fatty acid in pregnant women.

The results suggest a possible gene-nutrient interaction in plasma concentrations of n−3 PUFAS. The high intake of ALA and the LA/ALA ratio promoted increased ALA plasma concentrations in pregnant women homozygous for the minor alleles for polymorphisms rs174561 and rs3834458, but did not change the concentrations of desaturase, EPA, and DHA gene products.  Genetic variants of FADS1 and FADS2 genes may reduce gene transcription and enzymatic conversion rate of desaturases, which would result in enhanced amounts of n−3 long chain PUFAs precursor (ALA) and reduced amounts of products (EPA and DHA). The authors recommend the development of prospective studies in pregnant women to test the relationship between fatty acids and outcomes related to maternal and infant health. It was possible to observe that rs174561 (FADS1) and rs3834458 (FADS2) polymorphisms act as modifiers that affect in the relationship between ALA and LA/ALA ratio and the plasma concentrations of omega-3 polyunsaturated fatty acids in pregnant women. In homozygotes with the minor allele of rs174561 and rs3834458, increased ALA consumption does not favor the conversion of long-chain polyunsaturated fatty acids, EPA and DHA; however, low intake of the LA/ALA ratio may prevent plasma accumulation of ALA. It is possible that, in the pregnant women homozygous for minor alleles for polymorphisms rs174561 and rs3834458, the consumption of food sources with DHA is recommended, considering the probable occurrence of less gene transcription and enzymatic conversion. Regarding rs174575 SNP, plasma EPA concentrations were reduced in response to increased LA/ALA ratio consumption in pregnant women carrying the minor allele. Probably, the low intake of LA in relation to ALA intake is important to promote the adequate plasma profile of n−3 LCPUFAs in pregnant women.