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


METHODS
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 < or = 57.94%) compared with the highest quartile (methylation level > or = 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.
Wang
Li
L
Capital Institute of Pediatrics, Beijing, China.
Wang
Fang
F
Guan
Jing
J
Le
Jing
J
Wu
Lihua
L
Zou
Jizhen
J
Zhao
Huizhi
H
Pei
Lijun
L
Zheng
Xiaoying
X
Zhang
Ting
T
D000328:Adult; D001483:Base Sequence; D019175:DNA Methylation; D004522:Educational Status; D047108:Embryonic Development; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007118:Immunoassay; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics / Q000502:physiology*; D008297:Male; D044342:Malnutrition / Q000150:complications; D008969:Molecular Sequence Data; D009436:Neural Tube Defects / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010298:Parity; D011247:Pregnancy; D011248:Pregnancy Complications; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
D006710:Homocysteine; D014805:Vitamin B 12