Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy

Caroline L Relton, Craig S Wilding, Alison J Laffling, Pat A Jonas, Terry Burgess, Keith Binks, E Janet Tawn, John Burn

Research output: Contribution to journalArticle (Academic Journal)peer-review

70 Citations (Scopus)

Abstract

Previous studies have shown conflicting findings in linking polymorphic variation in folate-related genes to the risk of neural tube defect pregnancy. Recent evidence points to maternal genotype being important in determining NTD risk. A case-control study was undertaken in 97 mothers of NTD cases from the northern region of the UK. Pregnant controls (n = 190) from a regional DNA bank and non-pregnant controls (n = 100) from the same geographical area were recruited. MTHFR 677C >T, MTHFR 1298A >C, MTRR 66A >G, SHMT 1420C >T, CbetaS 844ins68, and RFC-1 80G >A allele and genotype frequencies were determined and odds ratios (OR) calculated. Erythrocyte folate levels for cases and controls were also measured and a comparison made of median erythrocyte folate levels stratified according to genotype. The MTHFR 677C >T variant was not shown to be an independent NTD risk factor in mothers of NTD-affected pregnancy. A second polymorphism in MTHFR, 1298A >C, was less frequently observed in mothers of NTD cases (OR [95% CI]=0.57 [0.33, 0.97]). Possession of compound 1298A >C and 677C >T variants elevated risk of NTD pregnancy considerably (TT/AC+TT/CC vs CC/AA OR [95% CI]=6.56 [1.10, 39.33]). Erythrocyte folate levels were persistently lower in NTD mothers (p = 0.001) despite assays being conducted many years after the index pregnancy (17.6+/-12.6 years). Erythrocyte folate levels were depressed in the presence of the MTHFR 677C >T variant.

Original languageEnglish
Pages (from-to)273-81
Number of pages9
JournalMolecular Genetics and Metabolism
Volume81
Issue number4
DOIs
Publication statusPublished - Apr 2004

Keywords

  • Adult
  • Case-Control Studies
  • Erythrocytes
  • Female
  • Folic Acid
  • Folic Acid Deficiency
  • Humans
  • Neural Tube Defects
  • Polymorphism, Genetic
  • Pregnancy
  • Pregnancy Complications
  • Risk Factors

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