Résumé:
Neural tube defects (NTDs) represent a major cause of infant mortality among congenital
malformations, whose pathogenesis remains poorly understood. In this study realized on an algerian
population of affected children and their mothers, we investigated the frequency of many
polymorphisms involved in the of folates / homocysteine metabolisms, Their possible contribution in
the etiology of NTDs, as well as their influence on folates and homocysteine concentrations.
The mutations were determined by the PCR / RFLP method, the assay of the biochemical
parameters was performed by chemiluminescence.
The analysis of genetic polymorphisms has shown that AG and AA variants of the G80A
polymorphism of the RFC gene are associated with the increased risk in affected children.
Moreover, we have observed that the combined effect of C677T and A1298C polymorphisms in
MTHFR gene, confers a risk for the occurrence of these abnormalities in our population .Indeed,
statistical test of interaction between the two polymorphisms have shown that the combination of
heterozygous genotypes(MTHFR 677CT/1298AC) elevate the risk in NTD cases (p <0.05).
These two polymorphisms ,in MTHFR gene, affects homocysteine metabolism in mothers of
NTD cases leading to homocysteine concentration values higher in mothers with TT genotype of the
C677T (p < 0.05) and that of AA genotype for the polymorphism A1298C (p <0.05).
For the polymorphism A2756G of the MTR gene, Although, Its association with NTDs risk
appears to be negative, It was found to decrease the RBC folate level strengthen the contribution of
A2756G mutation in NTDs occurrence (p <0.05).
Data on the association between MTRR A66G, CBS 844ins68 polymorphisms and plasma
homocysteine and serum/RBC folate concentrations as well as the relationship between this
polymorphisms and NTDs risk are inconclusive.
This original study by its primacy in Algeria and also in North Africa, both in terms of the
diversity of polymorphisms examined and the nature of the population (children affected) deserves,
encourages the extension of the study to a larger sample In order to show the interactive effect of these
mutations on the occurrence of NTDs and on the rate of metabolites.
