Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation

J Lipid Res. 2014 Jul;55(7):1245-53. doi: 10.1194/jlr.M045898. Epub 2014 May 19.

Abstract

Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥0.01 mM) and nonresponders (increase in plasma TG of ≥0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9-2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10(-5)), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond.

Keywords: fish oil; genetic risk score; nutrigenetics; responders; single nucleotide polymorphism.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dietary Supplements*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Triglycerides* / blood
  • Triglycerides* / genetics

Substances

  • Fatty Acids, Omega-3
  • Triglycerides