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

Abstract

BackgroundModulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear.MethodsIn 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.FindingsSignificant 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.InterpretationThis 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.

Effects of fish oil supplementation on glucose control and lipid levels among patients with type 2 diabetes mellitus: a Meta-analysis of randomized controlled trials

“…Genetic variants at PPARG associated with T2DM were only found in GWAS of Europeans but not in East Asians [35]. The effects of n-3 PUFA on blood lipids in type 2 diabetic patients may vary according to the genetic variations of CD36, NOS3 and PPAR-gamma genes, and personalized dietary recommendations based on certain genetic components to improve blood lipid profile may be extremely effective for n-3 PUFA intake [36].…”

Nutrigenetics, omega-3 and plasma lipids/lipoproteins/apolipoproteins with evidence evaluation using the GRADE approach: a systematic review

“…Again, these studies assessed relationships between a number of different genetic variants and study outcomes. In more recent years, several studies (n=8) used a nutri-GRS or polygenic approaches2 60–66 given the plausibility that many gene-lipid/lipoprotein/apolipoprotein and omega-3 interactions are polygenic in nature. Numerous studies assessed genetic variations in the FADS gene cluster,60 61 67–69 APOE, 60 69–78 CD36, 65 79 80 PPARγ2 (62,67,83–85 ) and PPARα 81–83.…”

“…In more recent years, several studies (n=8) used a nutri-GRS or polygenic approaches2 60–66 given the plausibility that many gene-lipid/lipoprotein/apolipoprotein and omega-3 interactions are polygenic in nature. Numerous studies assessed genetic variations in the FADS gene cluster,60 61 67–69 APOE, 60 69–78 CD36, 65 79 80 PPARγ2 (62,67,83–85 ) and PPARα 81–83. Among these studies, results related to significant gene–diet (omega-3) associations influencing lipid/lipoprotein outcomes were generally inconsistent except for APOE (rs429358 and rs7412), omega-3 and TG in males only,69–73 75–78 and for a 31-SNP nutri-GRS, omega-3 and TG 63 64.…”

Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: A pilot study

“…CD36 is a transmembrane protein expressed in various types of cells, including adipocytes, monocytes, macrophages, platelets, endothelial, and muscle cells [23,24]. This protein belongs to the scavenger receptor [23,25] and binds to lipoproteins, apoptotic cells, and long-chain fatty acids; thus, CD36 is also known as fatty acid translocase [23,26]. Coburn et al demonstrated that long chain fatty acid uptake and utilization have been defective in CD36 knockout mice [27].…”