The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy
| Autor: | R. Del Gado, Valeria Capra, Claudia Mandato, Maria Pia Sperandeo, Antonio Pepe, Elio Salvaggio, A. Buoninconti, Pierpaolo Mastroiacovo, R. de Franchis, Generoso Andria |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Threonine congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty 5 10-Methylenetetrahydrofolate Reductase (FADH2) Genotype Meta-Analysis as Topic Risk Factors Prevalence Genetics medicine Humans Point Mutation Cysteine Young adult Risk factor Child Spinal Dysraphism Methylenetetrahydrofolate Reductase (NADPH2) Genetics (clinical) Methylenetetrahydrofolate Dehydrogenase (NADP) Oxidoreductases Acting on CH-NH Group Donors biology Spina bifida Obstetrics business.industry Infant Newborn Case-control study Odds ratio Middle Aged medicine.disease Italy Case-Control Studies Methylenetetrahydrofolate reductase Attributable risk biology.protein Methylenetetrahydrofolate Dehydrogenase (NAD+) Oxidoreductases business Research Article |
| Zdroj: | Journal of Medical Genetics. 35:1009-1013 |
| ISSN: | 1468-6244 |
| DOI: | 10.1136/jmg.35.12.1009 |
| Popis: | 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. SUBJECTS: 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. SETTING: 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. |
| Databáze: | OpenAIRE |
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