C677T polymorphism of the 5,10-Methylenetetra-hydrofolate reductase [MTHFR] gene as a risk factor for neural tube defects among Egyptian families

ABSTRACT

Methylenetetrahydrofolate reductase [MTHFR] deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects [NTDs]. C677T MTHFR polymorphism is associated with NTDs, in some populations. Although the prevalence of this mutation has been reported from various ethnic populations, no data concerning Egyptian are available. C677T polymorphism was analyzed by PCR-RFLP. The frequencies of the C677T MTHFR polymorphism was determined in 35 case mothers, 19 case fathers and 9 children with NTDs compared with healthy 30 matched controls. In addition, allele and genotype frequencies were classified into different groups according to offspring NTD phenotype, consanguinity of the parents and number of affected offspring with NTD and or abortion. The prevalence of the polymorphic, homozygous [T/T] and heterozygous [C/T] C677T MTHFR genotypes were 6.3% and 38.1%, respectively, giving an allele frequency of 0.25. We observed increased frequency of heterozygotes of MTHFR in NTDs mothers versus the control although, C677T allele frequency was 0.28 in controls. Consanguinity rate was 45.7% among our families but it seems unlikely that it had an additional effect on the heterozygosity of the mutant genotype in this sample. In conclusion, neither homozygosity nor heterozygosity for the C677T polymorphism in the MTHFR gene constitute a genetic risk factor in the total NTDs but could be a risk of spina bifida aperta in this sample of Egyptian families. It is noteworthy to mention that this is the first report from Egypt evaluating the relationship between MTHFR677C>T and NTD