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Maternal Folate Genes and Aberrant DNA Hypermethylation among Offspring with Pediatric Lymphoblastic Leukemia

ABSTRACT: Pediatric acute lymphoblastic leukemia (ALL) is believed to originate in utero and frequently involves aberrant promoter methylation. Folate is the methyl donor for DNA methylation, suggesting that maternal folate metabolism may contribute to the development of ALL. We previously reported significant associations between single nucleotide polymorphisms (SNPs) in the maternal methionine synthase (MTR) gene and offspring’s risk of ALL. Here, we test the associations of 11 SNPs in MTR with aberrant DNA methylation in offspring with ALL. We recruited 51 ALL case-mother pairs from Texas Children’s Hospital from 2005-2010. We collected maternal saliva samples and diagnostic bone marrow plasma from cases. Bone marrow plasma was obtained from six healthy donors. DNA methylation was determined using MCA-Seq. Pyrosequencing was used to determine maternal MTR genotypes. We identified offspring with high and low promoter methylation and used logistic regression to estimate the effects of maternal genotype on offspring methylation. Twenty-two cases (43%) demonstrated high promoter methylation. Maternal MTR 113A>G was associated with aberrant DNA methylation in offspring (OR 4.59, 95% CI 1.21-17.93). To the best of our knowledge, this is the first report of an association between maternal genotype and offspring methylation in pediatric ALL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99793 | GEO | 2018/05/03

REPOSITORIES: GEO

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