Hypermethylation of AKT2 gene is associated with neural-tube defects in fetus.

Introduction: Neural-tube defects (NTDs) are common birth defects of complex etiology. Although many studies have confirmed a genetic component, the exact mechanism between DNA methylation and NTDs remains unclear.

Methods: In this work, we investigated the alteration of methylation from placental tissues obtained from 152 normal infants or with NTDs in 130 children with neural-tube defects. Genome-wide changes in DNA methylation were measured using the NimbleGen microarray. The expression levels of 12 genes were also determined, and two genes (AKT2 and CDC25C) showed low expression in NTDs by quantitative real-time PCR analysis. Then, the methyhlated region of AKT2 promoter sequences were confirmed by massARRAY.

Results: A total of 150 differentially methylated regions (81 low methylated regions and 69 high methylated regions) were selected by microarray. The expression levels of AKT2 and CDC25C showed lower expression in NTDs. And the percentage of methyhlated region of AKT2 promoter were increased in NTDs.

Conclusions: DNA mythelation was one of the possible epigenetic variations correlated with the occurrence of NTDs, and AKT2 may be a candidate gene for NTDs.