The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy

J Med Genet. 1998 Dec;35(12):1009-13. doi: 10.1136/jmg.35.12.1009.

Abstract

Objective: To estimate the risk for spina bifida associated with the common mutation C677T of the MTHFR gene in a country with a relatively low prevalence of NTDs.

Design: Case-control study.

Cases: 203 living patients affected with spina bifida (173 myelomeningocele and 30 lipomeningocele); controls: 583 subjects (306 young adults and 277 unselected newborns) from northern and central-southern Italy.

Cases: three spina bifida centres; young adult controls: DNA banks; newborn controls: regional neonatal screening centres.

Main outcome measures: Prevalence of the C677T genotypes in cases and controls by place of birth; odds ratios for spina bifida and estimated attributable fraction.

Results: The prevalence of T/T, T/C, and C/C genotype was 16.6%, 53.7%, and 29.7% in controls and 25.6%, 43.8%, and 30.6% in cases, respectively. We found no differences between type of defect or place of birth. The odds ratio for spina bifida associated with the T/T genotype v C/C plus T/C was 1.73 (95% CI 1.15, 2.59) and the corresponding attributable fraction was 10.8%. No increased risk was found for heterozygous patients (OR=0.79, 95% CI 0.53-1.18).

Conclusion: This study, as well as the meta-analysis we updated, shows that homozygosity for the MTHFR C677T mutation is a moderate risk factor in Europe, and even in Italy where there is a relatively low prevalence of spina bifida. The estimated attributable fraction associated with this risk factor explains only a small proportion of cases preventable by periconceptional folic acid supplementation. Thus, other genes involved in folate-homocysteine metabolism, their interaction, and the interaction between genetic and environmental factors should be investigated further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)
  • Adult
  • Case-Control Studies
  • Child
  • Cysteine / genetics*
  • Genotype
  • Humans
  • Infant, Newborn
  • Italy / epidemiology
  • Meta-Analysis as Topic
  • Methylenetetrahydrofolate Dehydrogenase (NAD+)
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Oxidoreductases
  • Oxidoreductases Acting on CH-NH Group Donors
  • Point Mutation*
  • Prevalence
  • Risk Factors
  • Spinal Dysraphism / enzymology*
  • Spinal Dysraphism / epidemiology
  • Spinal Dysraphism / genetics*
  • Threonine / genetics*

Substances

  • Threonine
  • Oxidoreductases
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Dehydrogenase (NAD+)
  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • Cysteine

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