Key Points
In an earlier systematic review, three genes (CD36, NOS3 and PPARG) showed interactions with omega-3 fatty acids to affect the levels of blood lipids. 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-3 fatty acid intervention for the blood lipids. In the present study, the interaction of genetic variants at CD36, NOS3 and PPARG were successfully replicated with omega-3 fatty acids on blood lipids. The T2D patients with CD36 major allele GG genotype, but not A allele carriers, displayed a decreased TG concentration in response to the omega-3 intervention. Carriers of the PPARG minor G allele, compared with those carrying CC genotype, showed increased levels of LDL-C among control group, but not among the omega-3 intervention group. An interaction between erythrocyte omega-3 fatty acid change and NOS3 variant on blood lipids was observed. rs1799983 minor A allele carriers responded better to high erythrocyte omega-3 fatty acid in improving lipid profiles. A genetic score generated based on the three SNPs demonstrated a combined effects of the three SNPs for their interactions with omega-3 supplements on blood lipids. The study suggests that rs1799983 minor A allele carriers might achieve more benefits in terms of improved lipids and other cardiovascular profiles in response to a higher omega-3 fatty acid exposure, compared to those with CC genotype. Dietary omega-3 fatty acid supplements could increase basal endothelial NO production and also increase NOS3 mRNA and protein levels. Moreover, omega-3 fatty acids were shown to regulate caveolar microenvironment, including the distribution and translocation of NOS in caveolar It is possible that omega-3 fatty acid supplements compensate the disrupted NOS3 activity caused by the rs1799983 minor A allele, whereas the homozygotes of the C major allele might not get additional benefit given its normal NOS3 activity in caveolar. The effects of omega-3 fatty acids on blood lipids may vary by genetic variation at CD36, NOS3, PPARG genes, and a personalized diet recommendation based on certain genetic make-up to improve blood lipid profiles may work specifically for omega-3 fatty acid intake. Nonetheless, this study is still quite preliminary, and more trials with larger sample size are warranted
ABSTRACT
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.
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