rs2524299 — FADS2

Intronic regulatory variant in FADS2 (Block 2 haplotype) that reduces basal FADS1 and FADS2 expression through a conserved intron 1 regulatory locus, impairing delta-6 desaturase activity and lowering circulating arachidonic acid, EPA, and DHA; captures an independent regulatory signal from the rs174568/rs174575 haplotype block

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FADS2 rs2524299 — An Independent Regulatory Signal for Delta-6 Desaturase

The FADS gene cluster on chromosome 11 contains dozens of variants that affect how efficiently your body converts short-chain dietary fats into long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid, EPA, and DHA. Most of these variants travel together in a single large block of linkage disequilibrium11 linkage disequilibrium
A genomic region where specific allele combinations are inherited together more often than expected by chance; variants in one LD block are effectively surrogates for each other. rs2524299 is notable because it does not belong to that primary block. It sits within a distinct regulatory region of FADS2 intron 1 — what researchers call Block 2 — and captures an independent regulatory signal that is not covered by the other FADS2 variants already on the platform (rs174568 and rs174575).

The Mechanism

rs2524299 is one of ten SNPs defining the Block 2 haplotype in FADS2 intron 1, a conserved locus containing predicted binding sites for SREBP and PPARγ22 SREBP and PPARγ
Sterol regulatory element binding protein and peroxisome proliferator-activated receptor gamma — two transcription factors that regulate lipid and fatty acid metabolism. Carriers of the minor haplotype (tagged by the T allele at rs2524299) show lower basal expression of both FADS1 and FADS2 in liver tissue. Because FADS2 encodes delta-6 desaturase (D6D) — the rate-limiting enzyme that initiates conversion of linoleic acid (LA) to gamma-linolenic acid (GLA), and alpha-linolenic acid (ALA) to stearidonic acid (SDA) — reduced expression compresses both the omega-6 and omega-3 elongation pathways simultaneously.

The result is the same substrate-product inversion seen across the FADS cluster: T allele carriers accumulate short-chain precursors (LA, ALA) while producing less of the long-chain end-products (arachidonic acid, EPA, DHA) for a given dietary intake.

Importantly, this Block 2 haplotype is not in linkage disequilibrium with the primary FADS cluster haplotype33 this Block 2 haplotype is not in linkage disequilibrium with the primary FADS cluster haplotype
Meaning that rs2524299 and rs174568 or rs174575 can be inherited independently; a person can carry both risk haplotypes simultaneously, or the Block 2 risk allele without the primary FADS risk allele. This independence means rs2524299 provides additive information about FADS2 regulation beyond what the other FADS2 variants in the database capture.

The Evidence

rs2524299 was examined alongside five other common FADS polymorphisms in the Costa Rica Study of fatty acid desaturase gene variants and myocardial infarction44 Costa Rica Study of fatty acid desaturase gene variants and myocardial infarction
Aslibekyan et al. 2012, Front Genet — 1,756 Costa Rican adults in a matched case-control design, with replication in the Nurses' Health Study and Health Professionals Follow-Up Study. Genetic variation across the FADS cluster — including rs2524299 — was associated with a robust linear decrease in adipose gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid. The minor allele consistently predicted lower concentrations of these long-chain products in adipose tissue fatty acid profiles.

An earlier Costa Rica Study analysis by Baylin et al. 200755 Baylin et al. 2007
alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction; Am J Clin Nutr examined 1,694 case-control pairs and found that FADS2 intron/promoter variants in this region were associated with lower adipose EPA and arachidonic acid, consistent with impaired ALA-to-EPA conversion. The intron 1 regulatory locus was specifically associated with variation in delta-6 desaturase activity.

The functional architecture of this regulatory locus was characterized by Reardon et al. 201266 Reardon et al. 2012
Insertion-Deletions in a FADS2 Intron 1 Conserved Regulatory Locus Control Expression of Fatty Acid Desaturases 1 and 2 and Modulate Response to Simvastatin; Prostaglandins Leukot Essent Fatty Acids, which showed that the Block 2 haplotype (containing rs2524299) controls basal expression of both FADS1 and FADS2 in liver cells. Minor haplotype homozygotes showed significantly lower basal FADS1 expression and, paradoxically, 20–40% greater upregulation of FADS1 and FADS2 in response to simvastatin — suggesting this locus participates in statin-mediated lipid regulation.

The broader evidence base for FADS cluster variants affecting LC-PUFA synthesis was confirmed in a systematic review of 132 studies including ~500,000 participants77 systematic review of 132 studies including ~500,000 participants
Visioli et al. 2026, Food Funct, showing that minor allele carriers across the FADS cluster show approximately 40–60% lower LC-PUFA conversion efficiency, with 14 studies demonstrating significant gene-by-diet interactions.

Practical Actions

For T allele carriers at rs2524299, the practical implication mirrors the other FADS2 impaired-conversion genotypes: plant-based omega-3 sources (flaxseed, chia, walnuts) supply ALA, but the first conversion step — ALA to stearidonic acid via FADS2 — is reduced by this haplotype. Preformed EPA and DHA from marine or algae-based sources bypass the impaired step entirely. TT homozygotes (the most impaired group, ~3% globally but ~17% in East Asian populations) should prioritize 2–4 g combined EPA+DHA daily; AT heterozygotes benefit from 1–2 g daily.

One clinically relevant interaction with medications: carriers of the Block 2 minor haplotype show enhanced FADS1 and FADS2 upregulation in response to statins and LXR agonists. This suggests that statin therapy may partially compensate for the reduced basal desaturase expression in this genotype — though this finding is preliminary and does not change the core supplementation strategy.

Interactions

rs2524299 is in linkage disequilibrium with rs2727270 and rs2727271 (Block 2 haplotype partners) but is independent of rs174568 and rs174575 (the primary FADS2 LD block). A person carrying T alleles at both rs2524299 and T alleles at rs174568 or rs174575 faces additive impairment of FADS2 expression from two independent regulatory mechanisms — a situation that would produce more severe LC-PUFA deficiency than either variant alone. Check related SNPs rs174568 and rs174575 for a full picture of your FADS2 regulatory status.

Nutrient Interactions

linoleic acid (LA) impaired_conversion
alpha-linolenic acid (ALA) impaired_conversion
arachidonic acid (AA) altered_metabolism
EPA increased_need
DHA increased_need

Genotype Interpretations

What each possible genotype means for this variant.

AA Normal D6D Regulatory Activity Normal

Normal FADS2 Block 2 regulation — no independent intron 1 risk signal

You carry two copies of the common A allele at rs2524299, associated with normal basal expression of FADS2 (delta-6 desaturase) through the Block 2 intron 1 regulatory locus. This independent regulatory haplotype contributes no additional reduction in your D6D enzyme levels beyond what your primary FADS2 haplotype (rs174568, rs174575) determines.

About 69% of people globally share this AA genotype, though it is more common in South Asians (~85%) and Europeans (~72%) and less common in East Asians (~35%) and Latinos (~56%). Your FADS2 regulation from this locus is unrestricted, meaning your capacity to convert plant-based omega-3 and omega-6 precursors into long-chain PUFAs is not impaired by this variant.

AT Reduced D6D Block 2 Activity Intermediate

One T allele — moderately reduced FADS2 expression from the Block 2 locus

The T allele at rs2524299 tags the minor Block 2 haplotype in FADS2 intron 1. This haplotype, present in about 24% of the population as a homozygous or heterozygous carrier, contains a conserved regulatory region with SREBP and PPARγ transcription factor binding sites that control basal FADS1 and FADS2 expression. Minor haplotype carriers show lower basal FADS gene expression in liver tissue, which translates to reduced delta-6 desaturase (D6D) enzyme activity and lower conversion of short-chain dietary precursors to LC-PUFAs.

Because rs2524299 is NOT in LD with rs174568 or rs174575 (the primary FADS2 variants), this locus provides additive information. AT carriers at rs2524299 who also carry risk alleles at rs174568 or rs174575 face compounded impairment of D6D expression from two independent regulatory mechanisms — a situation that warrants more aggressive preformed EPA/DHA supplementation.

TT Impaired D6D Block 2 Activity Poor Converter

Two T alleles — substantially reduced FADS2 expression from the independent Block 2 regulatory locus

The Block 2 haplotype containing rs2524299 controls basal FADS1 and FADS2 expression through a conserved regulatory element in FADS2 intron 1. TT homozygotes at rs2524299 carry the double dose of the minor haplotype and show the lowest basal expression of delta-6 desaturase among Block 2 genotypes. Because rs2524299 is not in linkage disequilibrium with the primary FADS2 variants rs174568 and rs174575, the Block 2 impairment is additive with any impairment from those variants.

The practical effect is that both the omega-3 pathway (ALA → SDA → EPA → DHA) and the omega-6 pathway (LA → GLA → DGLA → arachidonic acid) are more severely restricted than with either regulatory mechanism alone. Studies of the FADS cluster consistently show that individuals with the lowest FADS2 activity have the largest gap between dietary ALA intake and circulating EPA and DHA — a gap that increases progressively with each additional risk allele across independent LD blocks.

A secondary finding from the functional characterization of this locus is that minor haplotype homozygotes show paradoxically stronger upregulation of FADS1 and FADS2 in response to statins and LXR agonists (20–40% greater induction). This suggests statin therapy may partially compensate for the low basal desaturase expression — but this effect is preliminary and should not replace targeted dietary supplementation.