rs2727270 — FADS2

Intronic regulatory variant in FADS2; T allele carriers have lower D5D and D6D activity and reduced fasting insulin.

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FADS2 rs2727270 — The Desaturase Dimmer Switch

Deep in chromosome 11's FADS gene cluster, rs2727270 sits inside the first intron of FADS2.

The Evidence

Desaturase activity and PUFA composition. A cross-sectional study of 576 healthy Korean men11 cross-sectional study of 576 healthy Korean men
Kim et al. 2011, Nutrition and Metabolism, PMID 21513558 found that rs2727270 T allele carriers had significantly lower serum phospholipid proportions of DGLA (p=0.035) and arachidonic acid (AA, p<0.001), with higher linoleic acid (LA, p=0.026) — the signature of reduced D6D activity, which leaves the omega-6 precursor (LA) partially unconverted. The DGLA/LA ratio, a direct measure of D6D activity, was lower in T allele carriers, confirming the enzymatic bottleneck.

Longitudinal aging effects. A 3-year follow-up study of 122 nonobese Korean men aged 35–5922 3-year follow-up study of 122 nonobese Korean men aged 35–59
Kwak et al. 2013, Clinical Interventions in Aging, PMID 23818766 tracked how FADS genotypes influenced fatty acid trajectories over time. T allele carriers at rs2727270 maintained lower AA concentrations at both baseline (3.99% vs 4.73%, p=0.008) and 3-year follow-up (4.16% vs 5.42%, p=0.001), and showed a significantly attenuated increase in urinary 8-epi-PGF2α — a marker of oxidative stress — over the follow-up period (p=0.003). This lower oxidative stress trajectory in T allele carriers may reflect the reduced AA-derived pro-inflammatory eicosanoid production.

Insulin resistance. Notably, the Korean men's study also found that fasting insulin and HOMA-IR were significantly lower in rs2727270 T allele carriers compared to CC homozygotes — suggesting that reduced AA production and lower D5D/D6D activity may be protective against insulin resistance, at least in this population. This adds a nuanced dimension: the T haplotype's reduced desaturase activity has both costs (impaired EPA/DHA synthesis from plant precursors) and apparent benefits (lower AA-driven inflammation, lower insulin resistance).

Practical Actions

For CC homozygotes (the large majority): baseline desaturase activity is higher, but the well-documented omega-6:omega-3 imbalance of modern diets still means that relying on plant ALA alone is insufficient for optimal EPA and DHA status.

For CT and TT genotypes: reduced D5D and D6D activity means the conversion bottleneck from dietary LA to AA, and from ALA to EPA, is more pronounced. Preformed EPA and DHA from marine or algae sources bypasses both impaired steps. The lower AA production may also reduce pro-inflammatory eicosanoid output — a distinction that matters when selecting omega-3 supplementation targets.

Interactions

rs2727270 sits in a large linkage disequilibrium block with rs174537, rs174547, rs174575, rs174576, and rs2851682. However, studies in Mediterranean metabolic syndrome patients identified rs2727270 as a relatively independent association signal33 relatively independent association signal
unlike most top-ranked FADS SNPs which are highly correlated with lead SNP rs174547, rs2727270 showed lower LD with the lead signal in the GWAS by Coltell et al. 2020, PMID 31991592, suggesting it may capture unique functional variation beyond what the rs174537 or rs174547 loci explain. Carriers of multiple FADS risk alleles across the cluster face compounded reductions in desaturase activity.

Nutrient Interactions

omega-3 fatty acids (ALA) impaired_conversion
arachidonic acid (AA) altered_metabolism
eicosapentaenoic acid (EPA) increased_need

Genotype Interpretations

What each possible genotype means for this variant.

CC Full Desaturase Capacity Normal

Standard FADS2 activity — typical long-chain PUFA conversion

You carry two copies of the C allele at rs2727270. About 77% of people globally share this genotype (higher in African populations where C allele frequency exceeds 96%).

Even with standard desaturase capacity, the typical Western diet's high ratio of omega-6 to omega-3 still limits EPA and DHA status — but this is a dietary issue rather than a genetic conversion bottleneck.

CT Intermediate Desaturase Activity Intermediate

One T allele — mildly reduced FADS2 activity and lower arachidonic acid production

You carry one copy of the T allele at rs2727270. About 22% of people globally are CT heterozygotes (CT is more common in East Asian populations where the T allele reaches 34%). Research in Korean men found that T allele carriers had lower serum phospholipid arachidonic acid and DGLA than CC homozygotes, reflecting modestly reduced delta-6 desaturase (D6D) activity in the omega-6 pathway.

The same studies found that fasting insulin and HOMA-IR were lower in T allele carriers — suggesting the reduced AA production carries some metabolic benefit. Your capacity to synthesize EPA from plant-based ALA is also modestly reduced; preformed EPA from marine sources is a more reliable omega-3 source than flaxseed or walnuts for this genotype.

TT Reduced Desaturase Capacity Poor Converter

Two T alleles — substantially reduced FADS1 and FADS2 expression with impaired long-chain PUFA synthesis

There is a slower rate of conversion at two steps: (1) D6D converts linoleic acid (LA, 18:2 omega-6) to gamma-linolenic acid (GLA) and ALA to stearidonic acid — both of these are slowed; (2) D5D converts DGLA to arachidonic acid and ETA to EPA — also slowed. The net result: higher LA and lower AA in the omega-6 pathway, and slower ALA-to-EPA conversion in the omega-3 pathway.