rs174572 — FADS2

Intronic variant in FADS2 that reduces delta-6 desaturase activity, impairing the first rate-limiting step in converting dietary LA to GLA (omega-6) and ALA to stearidonic acid (omega-3), resulting in lower circulating EPA levels in T allele carriers

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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 desaturase11 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 activity22 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 cohort33 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 studies44 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 subjects55 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).

Nutrient Interactions

alpha-linolenic acid (ALA) impaired_conversion
linoleic acid (LA) impaired_conversion
eicosapentaenoic acid (EPA) increased_need

Genotype Interpretations

What each possible genotype means for this variant.

CC Efficient Converter Normal

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.

CT Intermediate Converter Intermediate

One T allele — moderately reduced FADS2 activity and lower EPA synthesis

The CT genotype produces a graded reduction in the overall PUFA conversion cascade. Because D6D is the rate-limiting first step, partial reduction in activity creates a bottleneck that propagates through both the omega-6 (LA → GLA → DGLA → AA) and omega-3 (ALA → SDA → EPA → DHA) pathways. The practical result: CT carriers accumulate more precursor fatty acids (LA, ALA, DGLA) in plasma while the downstream active forms (AA, EPA) are proportionally lower.

In dietary terms, this genotype makes plant-based omega-3 sources less effective. ALA from flax, chia, and walnuts must pass through the impaired D6D step before becoming EPA — a conversion rate already limited to <10% in people with normal FADS2 activity. In CT carriers, this rate is further reduced. Supplementation with preformed EPA bypasses this bottleneck.

TT Reduced Converter Poor Converter

Two T alleles — substantially impaired FADS2 activity and significantly lower EPA levels

The TT genotype at rs174572 produces the greatest reduction in FADS2 (delta-6 desaturase) activity across the three genotypes. D6D catalyzes the very first downstream step from dietary linoleic acid and ALA — without it, neither the omega-6 nor omega-3 pathway can progress efficiently.

In plasma, TT carriers show higher precursor pools (LA, ALA, DGLA) and lower products (GLA, stearidonic acid, and ultimately EPA). The D5D activity index — measured as the AA:DGLA ratio — falls by ~30% in TT compared to CC homozygotes in the HELENA data, representing a clinically meaningful reduction in overall PUFA synthesis capacity.

Critically, this cannot be compensated by eating more flaxseed. The ALA-to-EPA conversion rate in people with normal FADS2 activity is already below 10%; in TT carriers the impaired D6D step further reduces this, making plant-based ALA a functionally negligible source of EPA. Preformed EPA from marine or algae-based sources bypasses the blocked D6D gate entirely and is the only reliable strategy for maintaining adequate EPA tissue levels.