DNA Methylation Changes in Whole Blood and CD16+ Neutrophils in Response to Chronic Folic Acid Supplementation in Women of Childbearing Age.

Abstract

Folate, a water-soluble vitamin, is a key source of one-carbon groups for DNA methylation, but studies of the DNA methylation response to supplemental folic acid yield inconsistent results. These studies are commonly conducted using whole blood, which contains a mixed population of white blood cells that have been shown to confound results. The objective of this study was to determine if CD16+ neutrophils may provide more specific data than whole blood for identifying DNA methylation response to chronic folic acid supplementation. The study was performed in normal weight (BMI 18.5 - 24.9 kg/m2) women (18 - 35 y; n = 12), with blood samples taken before and after 8 weeks of folic acid supplementation at 800 μg/day. DNA methylation patterns from whole blood and isolated CD16+ neutrophils were measured across >485,000 CpG sites throughout the genome using the Infinium HumanMethylation450 BeadChip. Over the course of the 8-week supplementation, 6746 and 7513 CpG sites changed (p < 0.05) in whole blood and CD16+ neutrophils, respectively. DNA methylation decreased in 68.4% (whole blood) and 71.8% (CD16+ neutrophils) of these sites. There were only 182 CpG sites that changed in both the whole blood and CD16+ neutrophils, 139 of which changed in the same direction. These results suggest that the genome-wide DNA methylation response to chronic folic acid supplementation is different between whole blood and CD16+ neutrophils and that a single white blood cell type may function as a more specific epigenetic reporter of folate status than whole blood.