Abstract
A genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9–2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants’ blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.
Highlights
Cardiovascular diseases (CVD) are known to have several causes, including environmental and genetic predispositions
All single nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium (HWE). 87% of the genetic variability of IQ motif-containing J (IQCJ), as well as 85% of NXPH1, 96% of PHF17 and 100% of myeloblastosis viral oncogene homolog (MYB) were covered
Most of the SNPs were located in introns, except for three SNPs of PHF17 that were located in its upstream region, another of PHF17 that was in the three prime untranslated region (3 UTR) and one of MYB that was in its downstream region
Summary
Cardiovascular diseases (CVD) are known to have several causes, including environmental and genetic predispositions. Nutrition is an important environmental factor affecting the risk of developing CVD, and several dietary recommendations have been issued for prevention. These recommendations currently do not take into account the fact that individuals respond differently to dietary interventions this phenomenon is well documented in the literature [1]. In the European FINGEN study, 31% of participants who received a supplement of 1.8 g/day of ω-3 FA for eight weeks did not reduce their plasma triglyceride (TG) levels [3]. Our research group reported that 29% of all participants of the Fatty Acid Sensor (FAS) Study, who received ω-3 FA supplementation providing
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