Does FADS1 rs174537 influence omega-6 conversion to arachidonic acid?

The FADS1 gene plays a pivotal role in lipid metabolism, and its rs174537 single nucleotide polymorphism (SNP) is a primary genetic determinant of how the body processes dietary polyunsaturated fatty acids.

Genetic and enzymatic evidence

• Enzymatic modulation: The rs174537 polymorphism directly dictates delta-5 desaturase (D5D) expression and activity in a highly predictable, genotype-dependent manner.
• The G allele (High activity): Carriers of the major G allele (particularly GG homozygotes) exhibit elevated FADS1 expression and highly efficient D5D activity. This leads to rapid conversion of precursors, characterized by an elevated plasma arachidonic acid (ARA) to dihomo-gamma-linolenic acid (DGLA) ratio.
• The T allele (Low activity): The minor T allele correlates with reduced D5D expression. Homozygous TT carriers demonstrate impaired conversion, resulting in up to 25% lower circulating ARA levels and an accumulation of upstream precursors (linoleic acid and DGLA) compared to GG individuals.

Mechanistic pathways and inflammatory implications

• Rate-limiting conversion: D5D is the rate-limiting enzyme that catalyzes the direct biochemical conversion of the omega-6 precursor DGLA to ARA.
• Eicosanoid synthesis: Enhanced conversion to ARA in G allele carriers increases the cellular availability of the primary substrate required for the synthesis of bioactive, pro-inflammatory eicosanoids, including specific prostaglandins and leukotrienes, which can modulate systemic inflammatory pathways.

Bottom line

• The FADS1 rs174537 polymorphism strongly dictates the conversion efficiency of omega-6 precursors to arachidonic acid. GG carriers are highly efficient converters with elevated ARA and pro-inflammatory eicosanoid potential, whereas T allele carriers experience reduced D5D activity and lower circulating ARA.