title: The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.
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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  
  
  
  METHODS
  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.
  
  
  METHODS
  
  
  
  METHODS
  three spina bifida centres; young adult controls: DNA banks; newborn controls: regional neonatal screening centres.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics, Federico II University, Napoli, Italy.
authors.forename: R
authors.initials: R
authors.lastname: de Franchis
authors.forename: A
authors.initials: A
authors.lastname: Buoninconti
authors.forename: C
authors.initials: C
authors.lastname: Mandato
authors.forename: A
authors.initials: A
authors.lastname: Pepe
authors.forename: M P
authors.initials: MP
authors.lastname: Sperandeo
authors.forename: R
authors.initials: R
authors.lastname: Del Gado
authors.forename: V
authors.initials: V
authors.lastname: Capra
authors.forename: E
authors.initials: E
authors.lastname: Salvaggio
authors.forename: G
authors.initials: G
authors.lastname: Andria
authors.forename: P
authors.initials: P
authors.lastname: Mastroiacovo
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003545:Cysteine / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D015201:Meta-Analysis as Topic; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D010088:Oxidoreductases; D000587:Oxidoreductases Acting on CH-NH Group Donors; D017354:Point Mutation; D015995:Prevalence; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D013912:Threonine / Q000235:genetics*
chemical_list: D013912:Threonine; D010088:Oxidoreductases; D000587:Oxidoreductases Acting on CH-NH Group Donors; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+); D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D003545:Cysteine