RESUMO
BACKGROUND: Neural tube defects (NTDs) have been associated with biochemical factors involved in the conversion of homocysteine to methionine as folate deficiency and the mutation 677T in the N(5),N(10)-methylenetetrahydrofolate reductase gene (MTHFR). METHODS: A case-control study was performed to detect this mutation in 38 unrelated women with NTD deceased products and 31 mothers without antecedents of NTD offspring. All products were born in Nuevo León (northeastern Mexico) during 1997. Erythrocyte and plasmatic folate levels and the genotype of the 677 polymorphism at the MTHFR locus were analyzed in both groups. RESULTS: Although no significant differences were found in mean blood folate 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 vs. 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 analysis demonstrated a significantly higher proportion of 677T homozygous mothers with NTD products (39.6 vs. 9.1%, p <0.05). Allele frequencies for the 677T mutation were 0.55 and 0.36 for cases and controls, respectively. The odds ratio (OR) for having a NTD product was 6.1 (95%, CI 1.56-23.6) for homozygous 677T mothers vs. homozygous 677C and heterozygous mothers. Significantly 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 unfavorable genotype in mothers are important risk factors for severe NTD phenotype in our population.
Assuntos
Deficiência de Ácido Fólico/genética , Ácido Fólico/sangue , Defeitos do Tubo Neural/etiologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Complicações na Gravidez/enzimologia , Adulto , Alelos , Substituição de Aminoácidos , Anencefalia/etiologia , Anencefalia/mortalidade , Estudos de Casos e Controles , Códon/genética , Análise Mutacional de DNA , Eritrócitos/química , Feminino , Deficiência de Ácido Fólico/enzimologia , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/metabolismo , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Homocisteína/metabolismo , Humanos , Recém-Nascido , Masculino , Troca Materno-Fetal , Metilenotetra-Hidrofolato Redutase (NADPH2) , México/epidemiologia , Mutação de Sentido Incorreto , Defeitos do Tubo Neural/mortalidade , Gravidez , Resultado da Gravidez , Fatores de Risco , Disrafismo Espinal/etiologia , Disrafismo Espinal/mortalidadeRESUMO
OBJECTIVE: To evaluate the effect of weekly administration of 5 mg. folic acid (FA) intake on folic acid blood levels. MATERIAL AND METHODS: This concurrent comparative study was conducted in 1998, in urban and rural areas of Nuevo Leon State, Mexico. The study population consisted of 74 women who delivered a child during 1997, 39 of whom had a child with a neural tube defect. Women were given 5 mg. of folic acid, weekly for 3 months. Blood levels of folic acid were determined by radioimmunoassay (RIA) at baseline, and a week after taking the last folic acid dose. Data are presented as means and standard deviations. RESULTS: Ninety per cent of the women had significantly increased folic acid intraerythrocytary blood levels. Red cell folate increased from 150.49 +/- 31.17 ng/ml to 184.21 +/- 35.53 ng/ml (p < 0.005). Plasma folate increased from 5.93 +/- 1.98 ng/ml a 7.03 +/- 2.5 ng/ml (p < 0.05). Eighty-two per cent of women reached intracellular levels above 160 ng/ml. CONCLUSIONS: The weekly administration of folic acid is a simple and efficient method that could be used to supplement this vitamin to low-income populations. The English version of this paper is available at: http://www.insp.mx/salud/index.html.