INFLUENCE OF FADS1 AND FADS2 GENOTYPES ON MATERNAL DOCOSAHEXAENOIC ACID AND INFANT DEVELOPMENTAL STATUS
Scholtz, Susan Ann
University of Kansas
Dietetics & Nutrition
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FADS1 and FADS2 encode the rate-limiting enzymes responsible for arachidonic acid (ARA) and docosahexaenoic acid (DHA) synthesis. Single nucleotide polymorphisms (SNPs) in FADS1 and FADS2 influence the proportion of blood lipid and breast milk DHA, and breastfeeding confers an IQ-point advantage to children carrying the major allele for a SNP in FADS2. Previous studies have not examined the interaction between FADS genotypes and DHA supplementation, controlled for maternal DHA status to isolate the effect of FADS SNPs on breast milk DHA, or established whether maternal FADS genotypes influence infant cognition. This series of studies aimed to (1) elucidate the effect of DHA supplementation and FADS1 rs174553 and FADS2 rs174575 genotypes on red blood cell (RBC) ARA and DHA in a cohort of pregnant women, (2) determine if SNPs in maternal FADS1 and FADS2 influence the proportion of breast-milk DHA after controlling for the proportion of DHA in maternal RBCs, and (3) determine if toddler performance on the Bayley Scales of Infant Development Mental Development Index (BSID MDI) at 18 months is predicted by either maternal or child genotype in breastfed and formula-fed infants. The study population consisted of a subset of women enrolled in an NICHD-funded Phase-III clinical trial designed to determine the effects of consuming 600 mg/day of DHA throughout gestation on maternal and infant/toddler outcomes. Women provided blood and breast-milk samples the morning after and six weeks following parturition, respectively. Milk- and RBC-DHA were quantified by gas chromatography in comparison with weighed standards. Genomic DNA was extracted from buccal collection brushes, and genotyping performed with TaqMan SNP Genotyping Assays. MDI was assessed at 18 months of age. FADS1 minor allele homozygotes had a lower proportion of RBC-ARA and DHA than major-allele carriers (P ≤ 0.027) at enrollment. At delivery, minor allele homozygotes in the placebo group had a lower RBC-DHA than major-allele carriers (P ≤ 0.031), whereas women in the treatment group had similar RBC-DHA regardless of genotype (P = 0.941). Both FADS minor alleles were related to lower ARA among women assigned to the treatment group (P ≤ 0.029). RBC-ARA was not reduced in major allele homozygotes (P = 0.899). The concentration of breast-milk DHA was higher among women assigned to the treatment group than those assigned to the placebo (P < 0.001). However, when controlling for RBC-DHA to eliminate the influence of DHA supplementation and dietary intake, FADS2 minor allele homozygotes had a lower proportion of breast-milk DHA than major-allele carriers (P = 0.033). MDI was not related to maternal FADS1 or FADS2 genotypes. Finally, breastfed (but not formula-fed) infants carrying two copies of the FADS2 minor allele had a lower MDI at 18 months than major allele carriers (P = 0.007). Together, these results suggest that DHA supplementation compensates for the lower proportion RBC-DHA observed among FADS1 minor-allele homozygotes, but exaggerates the supplementation-associated reduction in RBC-ARA among FADS minor-allele carriers. They support the hypothesis that polymorphisms in FADS2 affect DHA in breast milk and confirm the previous observation that the FADS2 rs174575 genotype of the infant moderates the association between breastfeeding and a measure of cognition.
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