Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight

Abstract

Background: Specific single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene affect the activity and efficiency of enzymes that are responsible for the conversion of polyunsaturated fatty acids (PUFAs) into their long-chain active form. A high prevalence of SNPs that are associated with slow PUFA conversion has been described in Hispanic populations.

Objective: We assessed the heterogeneity of the effect of prenatal supplementation with docosahexaenoic acid (DHA) on birth weight across selected FADS SNPs in a sample of Mexican women and their offspring.

Design: We obtained information on the maternal genotype from stored blood samples of 654 women who received supplementation with 400 mg DHA/d or a placebo from weeks 18 to 22 of gestation through delivery as part of a randomized controlled trial conducted in Cuernavaca, Mexico. We selected 4 tag SNPs (rs174455, rs174556, rs174602, and rs498793) in the FADS region for analysis. We used an ANOVA to test for the heterogeneity of the effect on birth weight across each of the 4 SNPs.

Results: The mean ± SD birth weight was 3210 ± 470 g, and the weight-for-age z score (WAZ) was -0.24 ± 1.00. There were no intention-to-treat differences in birth weights. We showed significant heterogeneity by SNP rs174602 (P= 0.02); offspring of carriers of alleles TT and TC in the intervention group were heavier than those in the placebo group (WAZ: -0.13 ± 0.14 and -0.20 ± 0.08 compared with -0.55 ± 0.15 and -0.39 ± 0.09, respectively); there were no significant differences in offspring of rs174602 CC homozygotes (WAZ: -0.26 ± 0.09 in the intervention group compared with -0.04 ± 0.09 in the placebo group). We showed no significant heterogeneity across the other 3 FADS SNPs.

Conclusion: Differential responses to prenatal DHA supplementation on the basis of the genetic makeup of target populations could explain the mixed evidence of the impact of DHA supplementation on birth weight. This trial was registered at clinicaltrials.gov as NCT00646360.

Keywords: DHA; FADS; birth weight; long-chain PUFAs; prenatal supplementation.

FIGURE 1

Long-chain PUFA metabolism. Conversion from EPA to DHA requires elongation, desaturation (catalyzed by δ-6 desaturase), and β oxidation. Adapted from reference with permission.

FIGURE 2

Sample selection from the Prenatal Omega-3 Supplementation on Child Growth and Development original trial to the analytic sample for this study. FADS, fatty acid desaturase.

FIGURE 3

LD (D′) plot of 15 FADS SNPs. The value 1.0 denotes perfect LD between the SNP pair or 100% power. FADS, fatty acid desaturase; LD, linkage disequilibrium; r^2, r² power to detect LD; SNP, single nucleotide polymorphism.

FIGURE 4

Mean ± SEM birth WAZs relative to the WHO Growth Standards of 654 children whose mothers participated in the Prenatal Omega-3 Supplementation on Child Growth and Development trial by 4 tag FADS SNPs and prenatal DHA supplementation. *P-interaction < 0.05 after Bonferroni correction for multiple comparisons. FADS, fatty acid desaturase; SNP, single nucleotide polymorphism; WAZ, weight-for-age z score.