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

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