Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population

P. De Marco, M. Grazia Calevo, A. Moroni, L. Arata, E. Merello, R. H. Finnell, H. Zhu, L. Andreussi, A. Cama, V. Capra

Research output: Contribution to journalArticlepeer-review


Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggested that a defective methionine synthase (MS) enzyme could be a critical defect in folate-related NTDs. An A-to-G transition at bp 2756 on the MS gene has also been reported. In this case-control study, we studied the frequencies of these two polymorphisms in 203 Italian probands with non-syndromic NTDs: 98 mothers, 67 fathers, and 210 control individuals. Although the A1298C polymorphism is common in the Italian population (0.25), the allelic frequency was significantly higher among NTD cases and their parents. Heterozygous patients and mothers have an odds ratio (OR) of 1.98 and 2.11, respectively. The risk associated with the 1298CC genotype was higher for cases (OR = 3.67), for fathers (OR = 3.28), and, above all, for mothers (OR = 6.23). The prevalence of the A2756G polymorphism of the MS gene was determined (0.15). No increased prevalence of the mutated G allele was found in NTD families. This study shows that the MTHFR A1298C polymorphism is a genetic determinant for NTD risk in Italy. No association between the MS A2756G and NTD susceptibility was found.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalJournal of Human Genetics
Issue number6
Publication statusPublished - 2002


  • MS A2756G
  • MS gene
  • MTHFR A1298C
  • MTHFR gene
  • Neural tube defects

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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