EVALUATION OF THE MTHFR C677T ALLELE AND THE MTHFR GENE LOCUS IN A GERMAN SPINA-BIFIDA POPULATION

A number of recent studies have demonstrated that the occurrence and r ecurrence risk of neural tube defects (NTD) is reduced by folic acid s upplementation before and during pregnancy. Epidemiological studies ha ve shown low plasma folate and raised plasma homocysteine in women wit h spina bifida aperta (SB) children suggesting an abnormal folate meta bolism. The 5,10-methylenetetrahydrofolate reductase (MTHFR) variant C 677T, resulting in a decreased activity of the enzyme, has been associ ated with the development of NTD. Several studies demonstrated that ho mozygosity for the C677T mutation occurs at a higher frequency in pati ents with SE phenotype than in control individuals. The SE risk is str ongest if both the mother and her child have the mutation in the homoz ygous state. In the present study we compared the frequency of the C- and T-alleles in healthy German individuals (n = 153) with German SE p atients (n = 137). Our study groups reveal no significant difference i n C/T-allele frequencies and genotype distributions. A family based as sociation study, the transmission disequilibrium test, confirms the ab sence of an association between T-allele and SE. In 9 of 40 families w e were able to exclude linkage to the MTHFR locus (1p36.3) employing d ifferent inheritance models. Conclusion Our data show no evidence for an association between the C677T mutation and the occurrence of the SE phenotype. Therefore we cannot support the hypothesis that the MTHFR variant does account for a significant genetic predisposition to the S E phenotype in the studied German patients.