Abstract
Variants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children's genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells' derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother-children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children's cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children's FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children's FADS polymorphisms.
Highlights
There is consistent evidence that n-6 and n-3 long-chain (LC) PUFA are important to ensure optimal growth and development, during fetal and early postnatal life[1,2]
Different SNP influenced the DHA concentrations, but the model showed no statistical significance. This is the first study suggesting the presence of long-term effects of maternal prenatal supplementation with DHA and/or 5-MTHF on PUFA status and metabolism in the offspring at school age; our data seem to indicate an interaction between maternal supplementation during pregnancy and their offspring polymorphisms in the fatty acid desaturase (FADS) cluster, determining children’s PUFA concentrations in cheek cell GPL at school age
Previous results from Nutraceuticals for a Healthier Life (NUHEAL) study demonstrate clear associations between maternal fatty acids (FA) concentrations in plasma phospholipids during pregnancy and those levels found in their offspring[1], as well as changes depending on maternal supplementation during pregnancy
Summary
There is consistent evidence that n-6 and n-3 long-chain (LC) PUFA are important to ensure optimal growth and development, during fetal and early postnatal life[1,2]. Several studies have demonstrated the association between variants in the human genes FADS1, FADS2 and FADS3 and blood levels of PUFA in European or Caucasian populations[2,3,15,16,17,18] It seems that genetic variation in the FADS gene cluster could modify desaturase function supporting that minor alleles increase the concentrations of LA and ALA, and decrease the concentrations of AA, EPA, DPA and DHA in serum, plasma and erythrocytes. Glaser et al[15] found that FADS1 and FADS2 gene variants modulate tracking of serum PUFA levels in glycerophospholipids (GPL), which are the main lipid constituents of cell membranes with key functions in cell structure, intracellular signalling, anchoring to membranes and stabilisation of protein structure With these considerations in mind, we analysed the cheek cell GPL-FA composition in children from the Nutraceuticals for a Healthier Life (NUHEAL) study[22,23] at school age with the following aims:
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