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.
Highlights
We examined the interaction of genetic variants at CD36, NOS3 and PPARG with omega-3 fatty acid supplements on the change in blood lipids during the intervention based on the complete case analysis
The minor allele frequency of rs1527483 (A allele, CD36), rs1799983 (A allele, NOS3), and rs1801282 (G allele, PPARG) was 0.223, 0.073 and 0.057, respectively, and all single-nucleotide polymorphisms (SNP) were consistent with Hardy-Weinberg equilibrium (p N 0.05)
We successfully replicated the interaction of genetic variants at CD36, NOS3 and PPARG with omega-3 fatty acids on blood lipids
Summary
Corella et al [13] suggested that only three genes (CD36, NOS3 and PPARG) showed interactions with omega-3 fatty acids to affect the levels of blood lipids in the intervention studies, while no replication among trials has been reported so far. The aim of the present study was, to use a well-conducted randomized controlled trial to replicate the previous findings from intervention studies about the interaction of genetic variants (single-nucleotide polymorphisms, SNP) at CD36, NOS3 and PPARG with omega fatty acid intervention for the blood lipids. Findings: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (pinteraction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). 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
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