Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation

Abstract

Numerous meta-analyses have demonstrated that the long-chain n-3 PUFAs (LC n-3 PUFAs; EPA and DHA) signifi cantly reduce plasma TG levels in a dose-dependent manner, with the TG lowering being proportional to baseline levels ( 1, 2 ). In trials of subjects with high TG levels, n-3 PUFAs in dosages of 3.4-4.0 g/day decreased TG levels by 16% to 45% ( 1 ). However, there is well-recognized heterogeneity in the plasma TG response to LC n-3 PUFA supplementation ( 3 ): for example, 31% of all volunteers from the Fish Oil Intervention and Genotype (FINGEN) Study showed no reduction in TG after 1.8 g EPA and DHA per day for 8 weeks ( 4 ). Similarly, our research group has reported that 29% of all subjects showed no reduction Abstract Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥ 0.01 mM) and nonresponders (increase in plasma TG of ≥ 0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fi sh oil daily (1.9-2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders ( P < 1 × 10 ؊ 5 ), including SNPs in or near IQCJ-SCHIP1 , MYB , NELL1 , NXPH1 , PHF17 , and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI ( P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profi le than individuals who do not respond. -Rudkowska,

Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery

“…Our fi ndings of variable increases in n-3 plasma phospholipid fatty acid concentratations following supplementation are consistent with accumulating evidence for substantial variability in responses in circulating levels of n-3 PUFA following dietary supplementation ( 15,22,23 ). There is increasing interest in how such variation might be a determinant of the impact of n-3 PUFA on cardiovascular risk factors and clinical outcomes ( 24 ) because incorporation of n-3 PUFA into phospholipids could infl uence physical properties of cellular membranes and associated protein (e.g., ion channel) functions.…”

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

“…Conversely, subjects with higher GRS for glucose disorders had greater increases in fasting glucose when consuming a high-fat diet [32]. Moreover, a GRS built from genes identified by genome-wide association studies, partially explained the variation in triglyceride changes in response to omega-3 fatty acid supplementation [33]. …”

Novel Genetic Loci Associated with the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation

“…The whole study design and diets have been previously reported [10]. Briefly, subjects followed a run-in period of 2 weeks.…”

“…Methods to measure plasma lipids have previously been detailed [10]. Briefly, blood samples were collected after a 12-hour overnight fast and 48-hour alcohol abstinence.…”

“…Recently, a GWAS performed by our research group on subjects of the FAS study identified 13 SNPs associated with plasma TG levels [10]. A genetic risk score constructed with these loci explained 21.53% of the variability in plasma TG levels in response to an n-3 FA supplementation.…”