Folate levels and N-5,N-10-methylenetetrahydrofolate reductase genotype (MTHFR) in mothers of offspring with neural tube defects: A case-control study

Background. Neural tube defects (NTDs) have been associated with biochemica l factors involved in the conversion of homocysteine to methionine as folat e deficiency and the mutation 677T in the N-5,N-10- methylenetetrahydrofola te reductase gene (MTHFR). Methods. A case-control study was performed to detect this mutation in 38 u nrelated women with NTD deceased products and 31 mothers without antecedent s of NTD offspring. All products were born in Nuevo Leon (northeastern Mexi co) during 1997, Erythrocyte and plasmatic folate levels and the genotype o f the 677 polymorphism at the MTHFR locus were analyzed in both groups. Results. Although no significant differences were found in mean blood folat e levels, the percentage of women in the case group with erythrocyte folate levels <160 ng/mL was significantly higher than in the control group (75 v s. 51.2%, p <0.05). The proportion of women with plasma folate levels <3.5 ng/mL was higher in the case group (16.2 vs. 0%. p <0.01). Genotype analysi s demonstrated a significantly higher proportion of 677T homozygous mothers with NTD products (39.6 vs, 9.1%. p <0.05). Allele frequencies for the 677 T mutation were 0.55 and 0.36 for cases and controls, respectively. The odd s ratio (OR) for having a NTD product was 6.1 (95%, CI 1.56-23.6) for homoz ygous 677T mothers vs, homozygous 677C and heterozygous mothers. Significan tly low levels of erythrocyte folate were found in the 677C homozygous case group and in plasma folate in the 677C/677T heterozygous case mothers. Conclusions, Our study suggests that folate deficiency and MTHFR unfavorabl e genotype in mothers are important risk factors for severe NTD phenotype i n our population. (C) 2001 IMSS. Published by Elsevier Science Inc.