Objective: To investigate potential mechanisms underlying the associations previously identified by our group in a genome-wide association study (GWAS) between SNPs in four genes (IQCJ, NXPH1, PHF17 and MYB) and triglyceride (TG) levels following an omega-3 (n-3) fatty acid (FA) supplementation from marine source.

Methods: A total of 208 subjects received supplements of 3g/day of n-3 FA (1.9 - 2.2g of EPA and 1.1g of DHA) for six weeks. Plasma TG were measured before and after the supplementation. Using the HapMap database, the Haploview software and the Tagger selection algorithm, 67 SNPs were selected to cover ≥85% of the genetic variability of candidate genes. In silico analyses of RNA splicing, linkage disequilibrium, prediction of DNA affinity for transcription factors and expression were also performed. Analyses of DNA methylation and expression levels were respectively conducted on 30 and 35 participants’ blood samples with the Infinium HumanMethylation450 and Human-6 v3 expression arrays.

Results: The affinity of two SNPs in IQCJ (rs2595260 and rs9827242) for splicing sites was different according to the allele. Associations between 12 SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and methylation levels at CpG sites were found. Expression levels were influenced by genotype for two of these SNPs, namely one of NXPH1 (rs10486228) and one of MYB (rs17639758).

Conclusion: The plasma TG response to n-3 FA supplementation can be modulated by the effect of DNA methylation on expression levels of genes previously identified by GWAS.