ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

Abstract

Fish oil supplementation provides an inconsistent degree of protection from cardiovascular disease (CVD), which may be attributed to genetic variation. Single nucleotide polymorphisms (SNPs) in the elongation-ofvery-long-chain-fatty-acids-2 (ELOVL2) gene have been strongly associated with plasma proportions of n-3 longchain polyunsaturated fatty acids (LC-PUFA). We investigated the effect of genotype interaction with fish oil dosage on plasma n-3 LC-PUFA proportions in a parallel doubleblind controlled trial, involving 367 subjects randomised to treatment with 0.45, 0.9 and 1.8 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1.51:1) or olive oil placebo for 6 months. We genotyped 310 subjects for ELOVL2 gene SNPs rs3734398, rs2236212 and rs953413. At baseline, carriers of all minor alleles had lower proportions of plasma DHA than non-carriers (P = 0.021-0.030). Interaction between genotype and treatment was a significant determinant of plasma EPA (P \ 0.0001) and DHA (P = 0.004-0.032). After the 1.8 g/day dose, carriers of ELOVL2 SNP minor alleles had approximately 30 % higher proportions of EPA (P = 0.002-0.004) and 9 % higher DHA (P = 0.013-0.017) than non-carriers. Minor allele carriers could therefore particularly benefit from a high intake of EPA and DHA in maintaining high levels of plasma n-3 PUFA conducive to protection from CVD.

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

“…SNPs in Elovl2, which encode elongases 2, have also been shown to alter longer chain PUFA status. Minor alleles of SNPs in Elovl2 have been associated with lower DHA [77] and EPA [78] status. In addition, a SNP in Elovl5 has been shown to be associated with lower capacity to convert EPA to DPA [91] .…”

Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis

“…These studies have shown strong associations between the minor allele carriers of single nucleotide polymorphisms (SNPs) within FADS gene cluster, ELOVL2 and ELOVL5 and fatty acid levels in serum, plasma, red cells, breast milk and adipose tissue [13, 34–36]. …”

“…Major allele homozygotes of a 4 SNP haplotype showed more than 3-fold greater apparent conversion of [U- 13 C]-18:3n-3 to [U- 13 C]-20:5n-3 in plasma than minor allele carriers [44]. Al Saleh et al [36] found minor allele carriers of 3 SNP haplotype within the ELOVL2 gene with lower plasma 22:6n-3 than major allele carrier. An SNP within ELOVL5 was nominally associated with decreased capacity to metabolize 20:5n-3 to 22:5n-3 [35].…”

Genetic variants in ELOVL2 and HSD17B12 predict melanoma‐specific survival

“…GWAS have identified ELOVL2 variants to be associated with serum metabolic profile, aging process and DNA methylation . Recently, ELOVL2 rs3734398 has been reported to be significantly associated with plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement, which provides evidence on personalized dietary recommendations for reducing cardiovascular disease risk based on the genotype of this SNP . To date, ELOVL2 has not been reported to be associated with CM progression and prognosis.…”