An examination of polymorphic genes and folate metabolism in mothers affected by a spina bifida pregnancy

Citation
M. Lucock et al., An examination of polymorphic genes and folate metabolism in mothers affected by a spina bifida pregnancy, MOL GEN MET, 73(4), 2001, pp. 322-332
Citations number
30
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR GENETICS AND METABOLISM
ISSN journal
10967192 → ACNP
Volume
73
Issue
4
Year of publication
2001
Pages
322 - 332
Database
ISI
SICI code
1096-7192(200108)73:4<322:AEOPGA>2.0.ZU;2-H
Abstract
The effect of four polymorphic genes of folate-dependent methionine biosynt hesis have been investigated in mothers affected by a neural tube defect pr egnancy (NTD) and matched controls. The influence of the various genotypes on total red cell 5-methyl-H(4)folate, 5,10-methenyl-H(4)folate, and 5-form yl-H(4)folate is reported, as is the effect on homocysteine and radioassay folate in both serum and red cells. All of the single nucleotide polymorphi sms studied would seem to contribute to the cellular folate profile in some way. From the data presented, and from the work of others, it is likely th at C677T 5,10-methylenetetrahydrofolate reductase is the most important of these polymorphisms. Control mother folate profiles seem reasonably predict ive of any given methionine cycle mutation, but profiles in NTD mothers do not. On this basis, it seems likely that some other, as yet unidentified fo late lesion is causal for NTD. In NTD-C677T 5,10-methylenetetrahydrofolate reductase in particular, indexes of folate depletion such as high-performan ce liquid chromatography (HPLC) folate level, oligo-gamma -glutamyl chain l ength, homocysteine, and radioassay folate values all seem to deteriorate w ith increased mutant allele carriage. This indicates that this folate polym orphism may provide a critical threshold effect that helps to promote NTD o ccurrence in the presence of another, as yet unidentified folate-related fa ctor. In more general terms, on a by genotype basis, all I I genotypes stud ied give NTD mothers a higher homocysteine compared to controls. Furthermor e, a trend that is less universal indicates that NTD mothers have higher 5, 10-methenyl-H(4)folate and 5-methyl-H(4)folate levels and lower 5-formyl-H( 4)folate and H(4)PteGlu(1) levels than do controls. One of the most consist ent, and possibly specific, differences between participant groups is a sta tistically significant elevation of 5,10-methenyl-H(4)folate in NTD mothers (affects three genotypes). Possible interpretations of this finding are di scussed. (C) 2001 Academic Press.