Fatty Acid Desaturase Single Nucleotide Polymorphisms Modify the Effect of Prenatal Supplementation with Docosahexaenoic Acid on Birth Weight

Abstract

Maternal single nucleotide polymorphisms (SNP) in the Fatty Acid Desaturase genes (FADS) modulate the conversion of biologically inactive dietary polyunsaturated fatty acids (PUFA) into arachidonic and docosahexaenoic (DHA) acid, which are essential for fetal development. We assessed if four FADS SNPs (rs174445, rs174556, rs174602, rs498793) modified the association of prenatal DHA supplementation with birth weight (BW). 1,094 pregnant women in Cuernavaca, Mexico were randomized to supplementation with 400 mg/day of DHA or a placebo from 18‐22 w of gestation through delivery. We included 677 live births with maternal genotype information available (65% of the original sample). Mean (±SD) BW was 3,210 g (±466) and BW for gestational age z‐scores (WAZ) relative to the WHO Growth Standards was ‐0.24 (±1.00). There were no intent‐to‐treat differences in birth weight. We found a significant interaction by SNP rs174602 (p=0.02), where offspring of carriers of alleles TT and TC in the intervention group were heavier than those in the placebo (WAZ = ‐0.14±0.14 and ‐0.18±0.07 vs.‐0.55±0.14 and ‐0.40±0.8, respectively); while the opposite was observed among the offspring of rs174602 CC homozygotes (WAZ= ‐0.23±0.09 intervention vs. ‐0.02 ±0.08 placebo). We found no significant effect modification by the other three FADS SNPs. Differential responses to prenatal DHA supplementation trials based on target populations' genetic makeup and PUFA dietary intake could explain the mixed evidence of the impact of DHA on BW. Funded by NIH and the Nutricia Research Foundation.