Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation.
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 fish 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 profile than individuals who do not respond.
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
Iwona
I
Rudkowska
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
Frédéric
F
Guénard
Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
Pierre
P
Julien
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada.
Patrick
P
Couture
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada.
Simone
S
Lemieux
Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada Laboratory of Molecular Pharmacology, CHU de Québec Research Center, Quebec, Canada Faculty of Pharmacy, Laval University, Quebec, Canada.
Olivier
O
Barbier
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia Department of Nutrition.
Philip C
PC
Calder
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Anne Marie
AM
Minihane
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
Marie-Claude
MC
Vohl
D000328:Adult; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics
D015525:Fatty Acids, Omega-3; D014280:Triglycerides
fish oil; genetic risk score; nutrigenetics; responders; single nucleotide polymorphism