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 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.

Mycolic acid index susceptibility method for Mycobacterium tuberculosis.

A rapid drug susceptibility test to measure the susceptibility of Mycobacterium tuberculosis to isoniazid (INH) and rifampin (RIF) using clinical isolates and a newly defined mycolic acid index (MAI) was evaluated. A total of 200 clinical isolates of M. tuberculosis were tested for susceptibility or resistance to INH and RIF by the MAI susceptibility and indirect-proportion methods. Overall, there was agreement between the two methods for 398 (99.5%) of the 400 total tests. Specifically, the sensitivity of the MAI susceptibility method for INH and RIF was 97.6 and 100%, respectively. The specificity and positive predictive value were 100% for both drugs, and the negative predictive value for INH and RIF was 98.3 and 100%, respectively. In conclusion, the MAI susceptibility method described here can be used for rapid drug susceptibility testing of M. tuberculosis clinical isolates within 5 days after clinical isolates are incubated in the presence or absence of an antituberculosis drug.

[Impact of weekly administration of folic acid on folic acid blood levels]. / Efecto de la administración semanal de ácido fólico sobre los valores sanguíneos.

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.

[Folic acid levels, homocysteine and polymorphism of methylenetetrahydrofolate reductase enzyme (MTHFR) in patients with pre-eclampsia and eclampsia]. / Niveles de ácido fólico, homocisteína y polimorfismo de la enzima metilentetrahidrofolatorreductasa (MTHFR) en pacientes con preeclampsia severa y eclampsia.

UNLABELLED: Preeclampsia and eclampsia are the primary causes of maternal mortality. In the state of Nuevo León, from 1990 to 1998, these conditions represented 44.1% of maternal deaths. The presence of thrombogenic substances (homocysteine, C protein, and anticardiolipin antibodies) in the mother's blood has been related to this problem. The C677T polymorphism of the enzyme methylene tetrahydrofolate reductase (MTHFR) favors the increase of homocysteine levels, while folic acid (FA) supplementation decreases its levels. OBJECTIVE: To establish the role of FA in the physiopathology of preeclampsia in our environment. KIND OF STUDY: Longitudinal, prospective and comparative. CASES: Women with severe preeclampsia and/or eclampsia (n-13). CONTROLS: Women in the third trimester of a normal pregnancy (n + 15). 20 mL Blood samples were taken during the first 24 hours of puerperium, and their AF, homocysteine and MTHFR polymorphism were measured. The t Student test and the Exact Fisher test were used to compare between both groups. RESULTS: The values obtained for homocysteine were (x + SD): CASES: 9.85 micromoles/L + 2.88, and controls: 7.61 micromoles/L + 1.32 (p < 0.04). The frequency (%) of the genetic polymorphism for MTHFR was: positive homozygotes (T/T): 38.46 vs. 20, heterozygotes (C/T): 38.46 vs. 26.6, negative homozygotes (C/C): 23 vs 53, for cases and controls, respectively. CONCLUSIONS: According to our study, the frequency of the homozygote state (T/T) of MTHFR and increased blood levels of homocysteine is greater in women suffering from preeclampsia.