{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:34:04Z","timestamp":1787243644760,"version":"build-2736575974"},"reference-count":3,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,12]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/jmg.35.12.1009","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"1009-1013","source":"Crossref","is-referenced-by-count":50,"title":["The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy."],"prefix":"10.1136","volume":"35","author":[{"given":"R","family":"de Franchis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Buoninconti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Mandato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Pepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M P","family":"Sperandeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Del Gado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Capra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Salvaggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Andria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Mastroiacovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,12,1]]},"reference":[{"key":"ref_1","article-title":"Maximum likelihood estimate of odds ratios (OR) for the association between genotypes and case status were calculated with their exact mid-p 95% confidence interval (CI) using Epi6 software.20 OR heterogeneity among studies included in a meta-analysis was tested by the Breslow-Day test.2\" Pooled Mantel-Haenszel weighted OR was computed when heterogeneity was not statistically significant (p<0.05). The attributable fraction, representing the proportion of all cases in the target population that is attributable to the presence of the mutation(s), was estimated using the equation22: (AF= [fca (OR-1)]\/OR), where fc. is the fraction of cases with the genotype under study and OR is the odds ratio","unstructured":"Maximum likelihood estimate of odds ratios (OR) for the association between genotypes and case status were calculated with their exact mid-p 95% confidence interval (CI) using Epi6 software.20 OR heterogeneity among studies included in a meta-analysis was tested by the Breslow-Day test.2\" Pooled Mantel-Haenszel weighted OR was computed when heterogeneity was not statistically significant (p<0.05). The attributable fraction, representing the proportion of all cases in the target population that is attributable to the presence of the mutation(s), was estimated using the equation22: (AF= [fca (OR-1)]\/OR), where fc. is the fraction of cases with the genotype under study and OR is the odds ratio."},{"key":"ref_2","article-title":"between the homozygosity for the C677T mutation and spina bifida was causal, the proportion of all spina bifida cases that in the whole target population could be attributed to the presence of the homozygous C677T mutation was 8.5% or 10.8% depending on the comparison group used for the risk estimate (T\/T v C\/C only or T\/T v C\/C plus C\/T)","author":"Assuming that the association","unstructured":"Assuming that the association between the homozygosity for the C677T mutation and spina bifida was causal, the proportion of all spina bifida cases that in the whole target population could be attributed to the presence of the homozygous C677T mutation was 8.5% or 10.8% depending on the comparison group used for the risk estimate (T\/T v C\/C only or T\/T v C\/C plus C\/T)."},{"key":"ref_3","article-title":"Table 3 summarises the results of seven available studies including the present one.9'13 23 When possible, only data for spina bifida were considered (in the UK study'2 the NTD type was not specified) since four studies,9 10 23 including this one, did not include anencephaly, one found a higher risk for spina bifida than for other NTDs,\" and one found the 3 T\/T genotype only in 31 spina bifida cases and not in 12 anencephaly cases.'3 In other words, studies on the possible association between the MTHFR C677T mutation and NTDs seem to be based more on spina bifida than on other NTDs","unstructured":"Table 3 summarises the results of seven available studies including the present one.9'13 23 When possible, only data for spina bifida were considered (in the UK study'2 the NTD type was not specified) since four studies,9 10 23 including this one, did not include anencephaly, one found a higher risk for spina bifida than for other NTDs,\" and one found the 3 T\/T genotype only in 31 spina bifida cases and not in 12 anencephaly cases.'3 In other words, studies on the possible association between the MTHFR C677T mutation and NTDs seem to be based more on spina bifida than on other NTDs."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.12.1009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T18:53:07Z","timestamp":1759690387000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.12.1009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12]]},"references-count":3,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1998,12,1]]},"published-print":{"date-parts":[[1998,12]]}},"alternative-id":["10.1136\/jmg.35.12.1009"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.12.1009","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12]]}}}