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

Abstract

Background: A recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. Methods: A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. Results: In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Conclusion: Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation.

Docosahexaenoic Acid

“…Studies have shown that DHA supplementation in the maternal diet may have a favorable impact on the development of the infant's immune system and the risk of allergic or atopic diseases early in life (10). Recent studies also have identified polymorphisms in several genes that could partly explain the large interindividual variability observed in plasma TG concentrations in response to EPA plus DHA supplementation (11).…”

Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans

“…In our previous study, these SNPs were also found to exert significant gene-diet interactions modulating plasma TG levels [11]. These results therefore indicate that an individual’s genotype may possibly affect gene expression of IQCJ through the alteration of RNA splicing.…”

“…We increased the density of markers around GWAS-associated SNPs in the IQCJ , NXPH1 , PHF17 and MYB genes to further verify whether they are associated with plasma TG levels following ω-3 FA supplementation [11]. We found several effects of genotype and gene-diet interactions on plasma TG levels [11].…”

“…We increased the density of markers around GWAS-associated SNPs in the IQCJ , NXPH1 , PHF17 and MYB genes to further verify whether they are associated with plasma TG levels following ω-3 FA supplementation [11]. We found several effects of genotype and gene-diet interactions on plasma TG levels [11]. In the present study, we analysed gene expression and methylation levels, and conducted in silico analyses in order to better understand the potential underlying mechanisms by which IQCJ , NXPH1 , PHF17 and MYB interact with plasma ω-3 FA supplementation to modulate plasma TG levels.…”

“…Due to linkage disequilibrium (LD) between SNPs in neighbouring genes, it is difficult to discern actual causative SNPs solely with GWAS results. We therefore recently increased the density of markers at TG response-associated loci for the IQ motif-containing J ( IQCJ ), neurexophilin-1 ( NXPH1 ), PHD finger protein 17 ( PHF17 ) and V-Myb avian myeloblastosis viral oncogene homolog ( MYB ) genes, and found numerous gene-diet interactions and effects of SNPs in the IQCJ , NXPH1 and MYB genes on plasma TG levels [11]. However, the underlying mechanisms relating these genes and lipid metabolism remain unclear.…”