rs174568 — FADS2 FADS2 C>T (delta-6 desaturase)

FADS2 rs174568 — The Delta-6 Desaturase Bottleneck

Before your body can make the long-chain omega-3 and omega-6 fats that drive anti-inflammatory signaling, membrane integrity, and brain function, it must clear a biochemical bottleneck: the first desaturation step. The enzyme responsible is delta-6 desaturase (D6D)¹¹ delta-6 desaturase (D6D)
also called Δ6-desaturase; encoded by FADS2 on chromosome 11q12.2; the rate-limiting first step in both the omega-3 and omega-6 PUFA elongation cascades. Without adequate D6D activity, short-chain essential fats from plant foods — alpha-linolenic acid (ALA) from flaxseed and linoleic acid (LA) from most vegetable oils — cannot enter the elongation pathway and accumulate as unused precursors while downstream products like EPA, DHA, and arachidonic acid remain scarce.

rs174568 is an intronic variant in FADS2 that sits within a tightly linked haplotype block spanning the entire FADS gene cluster. The T allele tags a regulatory state associated with reduced FADS2 expression and lower delta-6 desaturase activity. Because D6D operates upstream of delta-5 desaturase (encoded by FADS1), reduced FADS2 activity compresses both fatty acid pathways simultaneously.

The Mechanism

Delta-6 desaturase catalyzes two rate-limiting reactions: - Omega-6 pathway: linoleic acid (LA, 18:2) → gamma-linolenic acid (GLA, 18:3n-6) - Omega-3 pathway: alpha-linolenic acid (ALA, 18:3n-3) → stearidonic acid (SDA, 18:4n-3)

Both GLA and SDA are then elongated before undergoing a second desaturation by delta-5 desaturase (FADS1), ultimately yielding arachidonic acid (AA), EPA, and DHA. The T allele at rs174568 impairs this first step. The result is accumulation of LA and ALA with reduced production of all downstream long-chain products. Critically, because this is the upstream bottleneck, even a normally functioning FADS1 cannot compensate — there is less substrate for it to work with.

The intronic location of rs174568 suggests a regulatory effect on FADS2 transcription rather than a coding change in the enzyme itself. The FADS cluster contains multiple SNPs in high linkage disequilibrium that collectively modulate expression levels of FADS1, FADS2, and FADS3, likely through shared regulatory elements and allele-specific methylation patterns.

The Evidence

rs174568 was included in a study of the FADS gene cluster in 224 individuals from Tangier Island²² study of the FADS gene cluster in 224 individuals from Tangier Island
Mathias et al. 2010, FADS genetic variants and omega-6 PUFA metabolism in a homogeneous island population, J Lipid Res, a genetically isolated European founder population providing a clean signal for variant effects. rs174568 was one of eight SNPs in strong linkage disequilibrium showing the same pattern: the minor allele consistently associated with decreased omega-6 PUFAs including arachidonic acid, with increased DGLA (the immediate precursor to AA). Effect sizes for the strongest FADS1-activity ratio associations reached p = 5.8 × 10⁻⁷ to 1.7 × 10⁻⁸.

A Bayesian genetic analysis in 761 Alaskan Eskimos Voruganti et al. 2012, Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases, Front Genet³³ Voruganti et al. 2012, Variants in CPT1A, FADS1, and FADS2 are associated with higher levels of estimated plasma and erythrocyte delta-5 desaturases, Front Genet identified rs174568 with posterior probability >0.8 for a functional effect on estimated delta desaturase activity. The finding was replicated in an independent Mexican American cohort, confirming cross-ancestry functional relevance.

The broader evidence for FADS cluster variants is substantial: a systematic review of 132 studies including ~500,000 participants⁴⁴ systematic review of 132 studies including ~500,000 participants
Visioli et al. 2026, Genetic modulation of omega-3 and omega-6 PUFA metabolism and health outcomes, Food Funct found that FADS1/FADS2 minor allele carriers show approximately 40–60% lower LC-PUFA conversion efficiency compared to common allele homozygotes, with 14 studies showing significant gene-by-diet interactions. At this effect size, plant-based omega-3 intake cannot reliably substitute for preformed EPA and DHA.

Practical Actions

For T allele carriers: plant-based omega-3 sources — flaxseed oil, chia seeds, walnuts — supply ALA, but the first conversion step (ALA → SDA via FADS2) is impaired. This makes preformed EPA and DHA from marine or algae sources the most reliable way to maintain adequate long-chain omega-3 status. TT homozygotes are most affected and should target 2–4 g combined EPA+DHA daily; CT heterozygotes benefit from 1–2 g daily.

For the omega-6 pathway, reduced GLA production means arachidonic acid synthesis from dietary linoleic acid is also impaired. While this sounds paradoxically protective (less AA = less pro-inflammatory eicosanoids), it also means cell membranes may be enriched with unconverted LA — a pattern associated with elevated triglycerides in some studies.

Monitoring triglyceride levels is warranted, particularly for TT homozygotes with diets high in refined omega-6 oils.

Interactions

rs174568 is in high linkage disequilibrium with multiple SNPs across the FADS1-FADS2-FADS3 cluster, including rs174537 (FADS1), rs174547 (FADS1), rs174575 (FADS2), and rs1535 (FADS2). Carriers of multiple minor alleles in this cluster experience compounding impairment at both the FADS2 (D6D) and FADS1 (D5D) steps — a complete blockade of the endogenous LC-PUFA synthesis pathway.

The functional consequence is similar to the neighboring FADS1 variants (rs174537, rs174547) already in the database, but operates at the earlier delta-6 step rather than delta-5, affecting a wider range of PUFA products. Both FADS2 and FADS1 minor allele carriers should prioritize preformed EPA/DHA over plant-based omega-3 sources.