Relationship of folate, vitamin B12 and methylation of insulin-like growth factor-II in maternal and cord blood

Background/Objective: One of the speculated mechanisms underlying fetal origin hypothesis of breast cancer is the possible influence of maternal environment on epigenetic regulation, such as changes in DNA methylation of the insulin-like growth factor-2 (IGF2) gene. The aim of the study is to investigate the relationship between folate, vitamin B-12 and methylation of the IGF2 gene in maternal and cord blood. Subjects/Methods: We conducted a cross-sectional study to measure methylation patterns of IGF2 in promoters 2 (P2) and promoters 3 (P3). Results: The percentage of methylation in IGF2 P3 was higher in maternal blood than in cord blood (P<0.0001), whereas the methylation in P2 was higher in cord blood than in maternal blood (P = 0.016). P3 methylation was correlated between maternal and cord blood (P<0.0001), but not P2 (P = 0.06). The multivariate linear regression model showed that methylation patterns of both promoters in cord blood were not associated with serum folate levels in either cord or maternal blood, whereas the P3 methylation patterns were associated with serum levels of vitamin B-12 in mother's blood (mean change (MC) = -0.22, P = 0.0014). Methylation patterns in P2 of maternal blood were associated with serum levels of vitamin B-12 in mother's blood (MC = -0.23, P = 0.012), exposure to passive smoking (MC = 0.46, P = 0.034) and mother's weight gain during pregnancy (MC = 0.23, P = 0.019). Conclusions: The study suggests that environment influences methylation patterns in maternal blood, and then the maternal patterns influence the methylation status and levels of folate and vitamin B-12 in cord blood. European Journal of Clinical Nutrition (2011) 65, 480-485; doi:10.1038/ejcn.2010.294; published online 19 January 2011