Relation between hypomethylation of long interspersed nucleotide elements and risk of neural tube defects  

Oleh:

Li, Wang ; Fang, Wang ; Jing, Guan ; Jing, Le ; Lihua, Wu

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 91 no. 05 (May 2010), page 1359-1367.
Topik: hypomethylation; nucleotide elements; neural tube defects

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2010.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Background: Impaired one-carbon metabolism is thought to be associated with the risk of neural tube defects (NTDs); however, the role of methylation in NTDs remains unclear. Long interspersed nucleotide element-1 (LINE-1) constitutes 17–25% of the human genome. LINE-1 hypomethylation correlates with global DNA methylation levels in cancerous cells, but limited information is available on LINE-1 methylation in NTDs. Objective: We determined whether LINE-1 methylation patterns were associated with neural tube development and the possible relations between DNA methylation and key maternal metabolites involved in folate-mediated one-carbon metabolism. Design: Global methylation, maternal plasma folic acid, vitamin B-12, and total homocysteine (tHcy) concentrations were assessed in 48 NTD and 49 control samples by immunoassay, and LINE-1 methylation levels were evaluated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Methylation levels of genomic DNA and LINE-1 decreased significantly in the neural tissue of NTD samples. The risk of NTDs increased with decreasing levels of LINE-1 methylation, with an odds ratio of 5.246 (95% CI: 1.519, 18.124; P = 0.009) for the lowest quartile (methylation level = 57.94%) compared with the highest quartile (methylation level = 60.94%). Compared with control subjects, case subjects had lower maternal plasma concentrations of vitamin B-12. Conclusions: Hypomethylation of LINE-1 and genomic DNA was associated with an increased risk of NTDs. Functional insufficiency of maternal plasma vitamin B-12 was associated with NTDs, although no significant correlation could be established between maternal folic acid, vitamin B, tHcy, and LINE-1 methylation.

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