Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial

EBioMedicine. 2018 May;31:150-156. doi: 10.1016/j.ebiom.2018.04.012. Epub 2018 Apr 17.


Background: Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear.

Methods: In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids.

Findings: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements.

Interpretation: This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles.

Keywords: Diabetes; Genetic variants; Interaction; Omega-3 fatty acids; Randomized controlled trial.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • CD36 Antigens* / genetics
  • CD36 Antigens* / metabolism
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Dietary Supplements*
  • Double-Blind Method
  • Epistasis, Genetic / drug effects*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Lipids / blood*
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III* / genetics
  • Nitric Oxide Synthase Type III* / metabolism
  • PPAR gamma* / genetics
  • PPAR gamma* / metabolism
  • Pregnancy


  • CD36 Antigens
  • Fatty Acids, Omega-3
  • Lipids
  • PPAR gamma
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III