(P21-006-25) High Prevalence of the FADS Indel I/I Genotype Among Black Women: A Secondary Analysis of the NAPS Trial

Objectives: Fatty acid desaturase 1 (FADS1) catalyzes the production of omega-6 Arachidonic Acid (ARA) from linoleic acid (LA). The FADS Indel is a 22-base pair I(nsertion)-D(eletion) (Indel) polymorphism that controls FADS1 expression, with circulating ARA increasing in the order D/D to I/D to I/I. As such, the FADS Indel genotype is likely highly relevant for characterizing an individual’s fatty acid status and informing the efficacy of fatty acid interventions.

We are working towards generating data on the prevalence of the FADS Indel I/II genotype across geographic ancestry groups. Using DNA from participants in the Assessment of DHA on Reducing Early preterm Birth (ADORE) trial, we provided the first genotype prevalence data on a U.S. population: Black participants were more likely to have the I allele and women with an I allele had higher rates of preterm births (Li et al., submitted, 2024). Using data from the thousand genome project (1kgp) we found that individuals from Africa and India were more likely to have the I allele than European or East Asian persons (in preparation).

The Nutrition and Pregnancy Study (NAPS) is an RCT of prenatal DHA supplementation to improve pregnancy health of Black women (n=168) living in low-resourced areas of Chicago. Our objective here is to test the hypothesis that the higher rate of I allele in FADS Indel is present in the NAPS cohort, replicating our previous findings.

Methods: Coded DNA samples from the NAPS participants were transferred to Texas for Indel determination via PCR using standardized protocols and gel electrophoresis according to established methods.

Results: Indel status was determined for 165 participants, stratified by genotype: D/D (16%, n = 27), I/D (47%, n = 77), and I/I (37%, n = 61). These findings are consistent with our past findings from the ADORE trial, with 36.2% (70/193) I/I among black participants.

Conclusions: The FADS Indel is a functional genotype that may drive ARA levels in some groups based on geographic ancestry. Further, the Indel differentiates those with higher or lower risk related to eicosanoid-driven health outcomes. We speculate that dietary changes to balance higher ARA, specifically with DHA or EPA supplementation, or possibly LA lowering, may be useful to reduce health risks in I allele carriers.

Funding Sources: R01HD084586