Abstract Background Individuals receiving a standardised daily dose of 2000 mg of the n -3 highly unsaturated fatty acid (HUFA) eicosapentaenoic acid (EPA) for 12 months in the seAFOod polyp prevention trial demonstrated wide inter-individual variability in red blood cell (RBC) EPA levels (expressed as % of total measured fatty acids). Eicosapentaenoic acid can be converted to n -3 docosapentaenoic acid ( n -3DPA) by the elongase elongation of very long-chain fatty acids (ELOVL) 2 . We tested whether single nucleotide polymorphisms (SNPs) in ELOVL2 (rs3734398, rs2236212, rs953413, rs3798713, rs9393903) are associated with differential RBC EPA and n -3DPA levels in seAFOod trial participants at baseline and while receiving EPA supplementation. Results Six hundred and three seAFOod trial participants had ELOVL2 genotype and RBC n -3 HUFA data. All five ELOVL2 SNPs were in strong linkage disequilibrium (R 2 > 0.95). Therefore, we focussed on rs953413 (genotype frequency: GG 30.8%, GA 50.1% and AA 19.1%), as the best characterised SNP, which is believed to be functional in human liver cells. Prior to trial intervention, minor (A) homozygotes displayed higher levels of n -3DPA ( P 0.05), in RBCs than major (G) allele carriers. The trend towards a greater increase in n -3DPA values in AA homozygotes during EPA treatment compared with GA heterozygotes or GG homozygotes did not reach statistical significance. There was also no significant difference in the change in RBC EPA or DHA levels during EPA treatment according to rs953413 genotype. Conclusions A secondary analysis of the seAFOod trial found that minor (A allele) homozygotes for the ELOVL2 SNP rs953413 have a higher baseline RBC n -3DPA level than G allele carriers. However, rs953413 genotype did not significantly influence ΔEPA, Δ n -3DPA, or ΔDHA levels during 6 or 12 months of high-dose EPA supplementation. Therefore, we do not provide evidence that genetic variation in ELOVL2 contributes to the inter-individual variability in the circulating EPA level associated with high-dose EPA supplementation.
Sun et al. (Thu,) studied this question.