title: Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects.
abstract: BACKGROUND
  Low maternal choline intake and blood concentration may be risk factors for having a child with a neural tube defect (NTD); however, the data are inconsistent. This is an important question to resolve because choline, if taken periconceptionally, might add to the protective effect currently being achieved by folic acid.
  
  
  OBJECTIVE
  We examined the relation between NTDs, choline status, and genetic polymorphisms reported to influence de novo choline synthesis to investigate claims that taking choline periconceptionally could reduce NTD rates.
  
  
  METHODS
  Two study groups of pregnant women were investigated: women who had a current NTD-affected pregnancy (AP; n = 71) and unaffected controls (n = 214) and women who had an NTD in another pregnancy but not in the current pregnancy [nonaffected pregnancy (NAP); n = 98] and unaffected controls (n = 386). Blood samples to measure betaine and total choline concentrations and single nucleotide polymorphisms related to choline metabolism were collected at their first prenatal visit.
  
  
  RESULTS
  Mean (±SD) plasma total choline concentrations in the AP (2.8 ± 1.0 mmol/L) and control (2.9 ± 0.9 mmol/L) groups did not differ significantly. Betaine concentrations were not significantly different between the 2 groups. Total choline and betaine in the NAP group did not differ from controls. Cases were significantly more likely to have the G allele of phosphatidylethanolamine-N-methyltransferase (PEMT; V175M, +5465 G>A) rs7946 (P = 0.02).
  
  
  CONCLUSIONS
  Our results indicate that maternal betaine and choline concentrations are not strongly associated with NTD risk. The association between PEMT rs7946 and NTDs requires confirmation. The addition of choline to folic acid supplements may not further reduce NTD risk.
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Aiyi
authors.initials: A
authors.lastname: Liu
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Barry
authors.initials: B
authors.lastname: Shane
authors.affiliation: From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM, RF, AL, and YW), and Genome Technology Branch, National Human Genome Research Institute (LCB), NIH, Bethesda, MD; the Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); the Health Research Board of Ireland, Dublin, Ireland (PNK); the University of California, Berkeley, Berkeley, CA (BS); and the Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland (AMM).
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
mesh_terms: D000328:Adult; D001622:Betaine / Q000097:blood; D016022:Case-Control Studies; D002794:Choline / Q000097:blood*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000097:blood; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D009436:Neural Tube Defects / Q000235:genetics*; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors; D012641:Selection, Genetic; D055815:Young Adult
chemical_list: D001622:Betaine; D005492:Folic Acid; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline