title: Folate, homocysteine and neural tube defects: an overview.
abstract: Folate administration substantially reduces the risk on neural tube detects (NTD). The interest for studying a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hcy levels in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate-dependent Hcy metabolism. Thus far, this has led to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with an increased risk of NTD and cause elevated Hcy concentrations. These levels can be normalized by additional folate intake. Thus, a dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies and also, in part, the protective effect of folate on NTD. Although the MTHFR polymorphisms are only moderate risk factors, population-wide they may account for an important part of the observed NTD prevalence.
authors.affiliation: Department of Pediatrics, University Medical Center Nijmegen, The Netherlands. N.vanderPut@ckslkn.azn.nl
authors.forename: N M
authors.initials: NM
authors.lastname: van der Put
authors.forename: H W
authors.initials: HW
authors.lastname: van Straaten
authors.forename: F J
authors.initials: FJ
authors.lastname: Trijbels
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
mesh_terms: D000818:Animals; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007408:Intestinal Absorption; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008956:Models, Chemical; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics* / Q000517:prevention & control; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)