Genetic and Non-Genetic Influences during Pregnancy on Infant Global and Site Specific DNA Methylation: Role for Folate Gene Variants and Vitamin B12

Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns

Epigenetic Epidemiology of Common Complex Disease: Prospects for Prediction, Prevention, and Treatment

As part of the PLoS Epigenetics Collection, Caroline Relton and George Davey Smith discuss the potential of epigenetics for the treatment and prevention of common complex diseases, including cancer

Integration of basic knowledge models for the simulation of cereal foods processing and properties

International audienceCereal processing (breadmaking, extrusion, pasting, etc.) covers a range of mechanisms that, despite their diversity, can be often reduced to a succession of two core phenomena: (1) the transition from a divided solid medium (the flour) to a continuous one through hydration, mechanical, biochemical, and thermal actions and (2) the expansion of a continuous matrix toward a porous structure as a result of the growth of bubble nuclei either by yeast fermentation or by water vaporization after a sudden pressure drop. Modeling them is critical for the domain, but can be quite challenging to address with mechanistic approaches relying on partial differential equations. In this chapter we present alternative approaches through basic knowledge models (BKM) that integrate scientific and expert knowledge, and possess operational interest for domain specialists. Using these BKMs, simulations of two cereal foods processes, extrusion and breadmaking, are provided by focusing on the two core phenomena. To support the use by non-specialists, these BKMs are implemented as computer tools, a Knowledge-Based System developed for the modeling of the flour mixing operation or Ludovic®, a simulation software for twin screw extrusion. They can be applied to a wide domain of compositions, provided that the data on product rheological properties are available. Finally, it is stated that the use of such systems can help food engineers to design cereal food products and predict their texture properties