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

• Published in: The American journal of clinical nutrition Vol. 91; no. 5; pp. 1359 - 1367
• Main Authors: Wang, Li, Wang, Fang, Guan, Jing, Le, Jing, Wu, Lihua, Zou, Jizhen, Zhao, Huizhi, Pei, Lijun, Zheng, Xiaoying, Zhang, Ting
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.05.2010; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: Adult; Base Sequence; Biological and medical sciences; Birth defects; blood; complications; Deoxyribonucleic acid; DNA; DNA Methylation; Educational Status; Embryonic Development; epidemiology; Feeding. Feeding behavior; Female; fetus; Fundamental and applied biological sciences. Psychology; genetics; Genome, Human; Genome, Human - genetics; Genomics; homocysteine; Homocysteine - blood; Humans; hypomethylation; Immunoassay; Long Interspersed Nucleotide Elements; Long Interspersed Nucleotide Elements - genetics; Long Interspersed Nucleotide Elements - physiology; Male; Malnutrition; Malnutrition - complications; maternal nutrition; Metabolism; Molecular Sequence Data; neural tube defects; Neural Tube Defects - blood; Neural Tube Defects - epidemiology; Neural Tube Defects - genetics; nucleotide sequences; nutrient intake; nutritional adequacy; Open Reading Frames; Open Reading Frames - genetics; Parity; physiology; Pregnancy; Pregnancy Complications; pregnant women; risk assessment; Risk Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B; Vitamin B 12; Vitamin B 12 - blood; Vitamins; Young Adult; Human; Nervous system diseases; Malformation; Diseases of the osteoarticular system; Risk factor; Nucleotide; Spine disease; Neural tube defect
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.2009.28858

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 [less-than or equal to] 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.