(OR30-04-24) The FADS Indel Modulates Arachidonic Acid Levels in Pregnancy and Identifies Responders From Non-responders in the ADORE Trial: A Precision Nutrition Post Hoc Analysis

Objectives: The ADORE trial was a three city randomized controlled trial of 200 mg/d (lo) or 1,000 mg/d (hi) DHA starting at 12-20 weeks gestation until labor commenced. Those on the higher dose had fewer early preterm births ( < 34 weeks gestation age (wGA)) than the lower dose, and the effect was stronger in those with lower entry DHA levels. We hypothesized that the 22 bp FADS insertion-deletion (Indel) would control circulating arachidonic acid (ARA) at baseline, as with other populations, and that higher ARA genotype (II) would have shorter gestational periods than for those with the lower ARA genotype (DD).

Methods: Buffy coat from the original trial participants (de-identified) from one center were transferred to Texas for analysis of indel status by PCR using standardized methods and gel electrophoresis. Once indel status was established, outcomes were provided to the Texas researchers for data analysis.

Results: Indel status was determined for n=337 participants, as follows (genotype, n, (dose)): D/D 83 (1,000), 63 (200); ID 64 (1,000), 86 (200); II 30 (1,000), 19 (200). At baseline, the FADS1 precursor-product ratio of 20:3 / 20:4 (DGLA to ARA) increased by 42% from DD to II, as expected from other populations, and surprisingly was independent of dose. Cord blood had an attenuated version of the same trend. Among the homozygotes, for low dose and DD, circulating DHA (%) was significantly related to wGA, otherwise neither circulating DHA nor ARA/DHA ratio had an effect on wGA. For high dose: for DD, ARA/DHA was not related to wGA at baseline or at post-partum (after dosing). In contrast, for II, baseline DHA was related to wGA and was stronger post-partum (r² = 0.38, p< 0.0004).

Conclusions: Precision nutrition based on the FADS indel genotype stratifies individuals into responders to 1,000 mg/d DHA with respect to gestational age at birth. All evidence collected to date indicates that the indel operates at the level of FADS1 (5-desaturase) mediating higher levels of circulating ARA and are consistent with the hypothesis that high dose DHA balances higher ARA and potentially more potent signaling for labor and delivery.

Funding Sources: NIH R01 HD083292