FADS2 rs174572 — The Delta-6 Desaturase Gatekeeper
Before your body can build the long-chain omega-3s and omega-6s it needs for every
cell membrane, every eicosanoid signal, and every synapse, it must pass dietary
fatty acids through a molecular gateway: delta-6 desaturase | FADS2 (fatty acid
desaturase 2) encodes delta-6 desaturase, the enzyme that inserts a double bond
at the Δ6 position in both the omega-3 and omega-6 pathways.
rs174572, an intronic variant in FADS2, alters how efficiently this gateway works.
The T allele is associated with reduced desaturase activity and measurably lower
circulating EPA — the omega-3 that drives anti-inflammatory eicosanoid production,
platelet function, and cardiovascular protection.
The Mechanism
Delta-6 desaturase catalyzes the first and rate-limiting step in two parallel pathways:
- Omega-6: linoleic acid (LA, 18:2n-6) → gamma-linolenic acid (GLA, 18:3n-6)
- Omega-3: alpha-linolenic acid (ALA, 18:3n-3) → stearidonic acid (SDA, 18:4n-3)
Without adequate D6D activity, dietary precursors accumulate (higher LA and ALA
in plasma) while downstream products (GLA, stearidonic acid, and ultimately EPA,
DHA, and AA) remain low. rs174572 sits in intron 1 of FADS2, and — consistent with
findings in the broader FADS locus — likely affects FADS2 promoter methylation and
transcriptional activity | Allele-specific methylation at FADS cluster intronic
and promoter CpG sites has been confirmed in multiple tissues; intronic SNPs in high
LD with the cluster tag this regulatory effect.
T allele carriers produce less FADS2 enzyme, throttling both pathways simultaneously.
The Evidence
The most direct evidence comes from a genome-wide fatty acid study of 1,144 European
adolescents in the HELENA cohort | Bokor et al. J Lipid Res 2010; 51:2325–2333;
13 FADS SNPs genotyped across 9 European countries.
Carriers of the minor T allele at rs174572 showed significantly higher plasma LA
(p=0.0009), higher ALA (p=0.0002), and higher DGLA — precursors that had not been
converted downstream. Simultaneously, arachidonic acid was lower (p<1×10⁻⁶) and
EPA was substantially lower (p=4.2×10⁻⁶). The D5D activity index (which reflects
the overall efficiency of the cascade) fell from 3.70 in CC homozygotes to 3.06 in
CT heterozygotes and 2.60 in TT homozygotes (p=6.1×10⁻³¹) — one of the strongest
genotype-to-enzyme associations observed in the FADS gene cluster.
A 2024 scoping review of 40 studies | Loukil, Mutch & Plourde, Genes Nutr 2024;
DOI: 10.1186/s12263-024-00747-4
confirmed that minor allele carriers of rs174572 have lower circulating EPA, placing
this SNP among the FADS variants with documented EPA-specific associations.
The cardiovascular relevance of FADS-driven PUFA imbalances is documented in a
study of 876 subjects | Martinelli et al. Am J Clin Nutr 2008
where a high AA-to-LA ratio (reflecting high D5D activity, the opposite of what T
allele carriers have) independently predicted CRP elevation and coronary artery
disease risk (OR ~2.55). For T allele carriers, the clinical concern is the mirror
image: chronically low EPA results in reduced production of anti-inflammatory
eicosanoids (prostaglandin E3, thromboxane A3) and inadequate cardiovascular protection
from omega-3 signaling — without the genetic test, this functional deficiency is
invisible.
Practical Actions
Because D6D activity is the first committed step in PUFA synthesis, T allele carriers
cannot compensate by eating more flaxseed, chia, or walnuts. Those sources supply
ALA, which still must pass through the impaired D6D gate before becoming stearidonic
acid, EPA, or DHA. The only reliable route to adequate EPA is preformed EPA from
marine or algae sources that bypass the conversion step entirely.
For TT homozygotes — the most affected genotype — supplementation with 2–4 g combined
EPA+DHA daily from concentrated fish oil or algae-based sources is the most targeted
approach. For CT heterozygotes, 1–2 g daily represents a reasonable starting point.
The omega-3 index (erythrocyte EPA+DHA percentage) provides a direct, individualized
measure of whether supplementation is achieving adequate tissue levels.
Interactions
rs174572 is located near rs174547, rs174546, rs174537, rs174575, and rs174589 in the
FADS gene cluster on chromosome 11q12.2. These variants co-segregate as haplotype
blocks, and carrying T alleles across multiple FADS cluster SNPs compounds the
reduction in overall PUFA conversion capacity. The functional impact is therefore
greater in individuals who carry risk alleles at both FADS2 (rs174572, D6D — the
first step) and FADS1 (rs174537 or rs174547, D5D — the downstream step), as both
desaturase steps become rate-limited simultaneously. This combination represents
a proposal for a compound action (see harvesting notes).
Alla genotyper
Normal FADS2 activity — full delta-6 desaturase function
You carry two copies of the C allele at rs174572, the common reference genotype associated with normal delta-6 desaturase (FADS2) activity. About 65% of the global population and approximately 57% of Europeans share this genotype. Your FADS2 enzyme efficiently performs the first rate-limiting step in converting dietary linoleic acid (omega-6) into GLA and arachidonic acid, and alpha-linolenic acid (omega-3) into stearidonic acid and ultimately EPA. This means plant-based omega-3 sources such as flaxseed, chia, and walnuts provide a meaningful — though not complete — contribution to your EPA levels. Marine sources of preformed EPA and DHA still provide the most efficient pathway, but you are not genetically impaired in your conversion capacity.
One T allele — moderately reduced FADS2 activity and lower EPA synthesis
You carry one copy of the T allele at rs174572. In the HELENA cohort study of 1,144 European adolescents, heterozygotes showed intermediate D5D activity (mean 3.06, SD 0.81) compared to CC carriers (mean 3.70, SD 1.09), with significantly higher levels of the precursor fatty acids LA and ALA in plasma and correspondingly lower arachidonic acid and EPA. About 31% of the global population carries this CT genotype. One T allele partially reduces FADS2 (delta-6 desaturase) expression. This means plant-sourced ALA converts to EPA less efficiently than in CC homozygotes. Relying on flax, chia, or walnuts as your primary omega-3 strategy will leave you with lower EPA than someone with CC carrying the same diet.
Two T alleles — substantially impaired FADS2 activity and significantly lower EPA levels
You carry two copies of the T allele at rs174572. In the HELENA cohort study, TT homozygotes showed substantially reduced D5D activity (mean 2.60, SD 0.69 vs. 3.70, SD 1.09 in CC carriers; p=6.1×10⁻³¹), with significantly elevated plasma linoleic acid and alpha-linolenic acid (precursors that were not converted downstream) alongside markedly lower arachidonic acid and EPA. This is about 4% of the global population and approximately 6% of Europeans. Both your omega-3 and omega-6 conversion pathways are impaired at the first rate-limiting step. Plant-sourced omega-3 fatty acids (ALA from flax, chia, walnuts) are substantially less useful for you than for people with normal FADS2 activity. You need direct supplementation with preformed EPA to maintain adequate omega-3 status. Without it, chronically low EPA means reduced production of anti-inflammatory eicosanoids and impaired cardiovascular protection from the omega-3 pathway.