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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.

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Zheng, Ju-Sheng 
Chen, Jiewen 
Wang, Ling 
Yang, Hong 
Fang, Ling 


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.



Diabetes, Genetic variants, Interaction, Omega-3 fatty acids, Randomized controlled trial, Aged, CD36 Antigens, Diabetes Mellitus, Type 2, Dietary Supplements, Double-Blind Method, Epistasis, Genetic, Fatty Acids, Omega-3, Female, Genetic Variation, Genotype, Humans, Lipids, Male, Middle Aged, Nitric Oxide Synthase Type III, PPAR gamma, Pregnancy

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Elsevier BV
Medical Research Council (MC_UU_12015/5)
MRC (unknown)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701708)