DNA methyltransferase candidate polymorphisms, imprinting methylation, and birth outcome

Abstract
BACKGROUND: Birth weight and prematurity are important obstetric outcomes linked to lifelong health but the causal connections between these, and the factors that affect them, are not well understood. We studied a large birth cohort to look for evidence of epigenetic involvement in birth outcomes. METHODS: We investigated the association between birth weight, length, placental weight and duration of gestation and variants in four genes involved in DNA methylation in 1,236 mothers and 1,073 newborns. We measured DNMT1 (rs2162560), DNMT3A (rs734693), DNMT3B (rs2424913) and DNMT3L (rs7354779). RESULTS: The minor DNMT3L allele was associated with higher birth weight (+54 95%CI 10,99 g ; p=0.016), birth length (+0.23 95%CI 0.04,0.42 cm; p=0.017), placental weight, (+18 95%CI 3,33 g; p=0.017), and lower risk of being in the lowest birth weight decile (OR 0.63 95%CI 0.42,0.92; p=0.018) or requiring neonatal care (OR 0.72 95%CI 0.54,0.98; p=0.034). The DNMT3B rare allele in the mother was associated with a an almost a doubling of the risk of prematurity (<37 weeks gestation); (OR 1.95 95%CI 1.30,2.94; p=0.001). CONCLUSIONS: These results are consistent with epigenetic regulation of birth size and length of gestation. We speculate that imprinting may be the epigenetic mechanism and that environmental effects such as diet could influence the process. Further investigation of epigenetic control of birth size and linked health outcomes in later life, and the factors that influence them, are merited. There may be value in investigating the role of these variants in adult health outcomes linked to birth weight.
Year
2013
Category
Refereed journal
Output Tags
SG 2006-2011 P4 Human Health - Miscellaneous