Peripheral Blood DNA Methylation Changes after Omega-3 Fatty Acid Treatment Indicate Anti-inflammatory Effects and Individual Variability

BackgroundOmega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits based on potential anti-inflammatory effects. However, the factors involved in mediating the anti-inflammatory responses to n-3 PUFAs are not fully understood; furthermore, many effects from n-3 PUFA treatment are not well characterized in humans. Of interest is the role of DNA methylation (DNAm) in mediating the effects of n-3 PUFAs on inflammation. ObjectiveWe aimed to characterize the effects of n-3 PUFA treatment on DNAm in inflammation-related signaling pathways in PBMCs of women at high risk of breast cancer MethodsPBMCs of women at high risk of breast cancer were obtained at 0 and 6 months of n-3 PUFA treatment in a previously reported dose finding trial (n=10 matched pairs in the 5 g/day EPA+DHA dose arm).[53] DNA methylation of PBMCs were assayed using reduced representation bisulfite sequencing to obtain genome-wide methylation profiles on a single nucleotide level. Analyses were performed to investigate the effects of n-3 PUFA treatment on DNAm both genome-wide and within a set of candidate genes. ResultsA large number of differentially methylated CpGs (DMCs) in gene promoters (24,842 DMCs in 5507 genes) showed significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Using these DNAm changes, pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor pathway. Based on analyses of data per individual, DNAm changes from n-3 PUFA treatment appear highly variable between study participants. ConclusionsDietary n-3 PUFA supplementation for six months is associated with DNAm changes in PBMCs with potential for anti-inflammatory effects. PBMC DNAm profiles may offer a novel means of assessing individual response to n-3 PUFAs. This observation warrants further investigation in future n-3 PUFA intervention studies.