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Background: Maternal serum concentrations of folate, homocysteine, and vitamin B12 have been associated with pre-eclampsia. Nevertheless, reported studies involve limited number of cases to reliably assess the nature of these associations. Our aim was to examine the relation of these three biomarkers with pre-eclampsia risk in a large Colombian population., Materials and Methods: Design: A case-control study. Setting: Cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight different Colombian cities between 2000 and 2012. Population or Sample: 2978 cases and 4096 controls were studied. Maternal serum concentrations of folate, homocysteine, and vitamin B12 were determined in 1148 (43.6%) cases and 1300 (31.7%) controls. Also, self-reported folic acid supplementation was recorded for 2563 (84%) cases and 3155 (84%) controls. Analysis: Adjusted odds ratios (OR) for pre-eclampsia were estimated for one standard deviation (1SD) increase in log-transformed biomarkers. Furthermore, we conducted analyses to compare women that reported taking folic acid supplementation for different periods during pregnancy. Main Outcomes Measures: Odds ratio for pre-eclampsia., Results: After adjusting for potential confounders in logistic regression models, the OR for pre-eclampsia was 0.80 (95% CI: 0.72, 0.90) for 1SD increase in log-folate, 1.16 (95%CI: 1.05, 1.27) for 1SD increase in log-homocysteine, and 1.10 (95%CI: 0.99, 1.22) for 1SD increase in log-vitamin B12. No interactions among the biomarkers were identified. Women who self-reported consumption of folic acid (1 mg/day) throughout their pregnancy had an adjusted OR for pre-eclampsia of 0.86 (95%CI: 0.67, 1.09) compared to women that reported no consumption of folic acid at any point during pregnancy., Conclusions: Maternal serum concentrations of folate were associated as a protective factor for pre-eclampsia while concentrations of homocysteine were associated as a risk factor. No association between maternal vitamin B12 concentrations and preeclampsia was found., Competing Interests: The authors have declared that no competing interests exist.

Background: Nitric oxide (NO) synthesized by endothelial cells is known to be a potent vasodilator. It has been suggested that polymorphisms in endothelial nitric oxide synthase (eNOS) can affect the response of the vascular endothelium to increased oxidative stress. The objective of the present study was to determine the presence of G894T (rs1799983), intron-4 (27-bp TR) and -T786C (rs2070744) polymorphisms in the eNOS gene among the Colombian general population., Results: Genotype and allele frequencies showed significant differences in their distribution. White, black and mixed populations were in HW equilibrium for the variants in 27-bp TR- and rs1799983, but the black population was in HW disequilibrium for rs2070744 (p < 0.001). Allele "T" of rs1799983 polymorphisms was more common in the white population (26,5%) than the others, while allele "C" of rs2070744 polymorphisms had a similar frequency in all populations, and the allele 4a from 27-bp TR was more frequent in the black population (26,2%) than the others. Similar differences were found when genotypes were analyzed., Conclusion: The findings suggest that there is a substantial difference in the distribution of eNOS polymorphisms between different ethnic groups. These results could aid the understanding of inter-ethnic differences in NO bioavailability, cardiovascular risk, and response to drugs.

Polymorphisms in the endothelial NO synthase (eNOS) gene have been evaluated as risk factors for preeclampsia. However, data from small studies are conflicting. We assessed whether eNOS genotypes alter the risk of preeclampsia in a population in which the incidence of this disorder is high. A total of 844 young pregnant women (322 preeclamptic and 522 controls) were recruited from 5 cities. Genotyping for the Glu298Asp, intron-4 and -786T-->C polymorphisms in the eNOS gene was conducted. Multivariate odds ratios (ORs) were obtained to estimate the association of individual polymorphisms and haplotypes with preeclampsia risk. No increase in the risk of preeclampsia for the intron-4 or -786T-->C polymorphisms was observed under any model of inheritance. In contrast, in women homozygous for the Asp298 allele, the adjusted OR for preeclampsia was 4.60 (95% confidence interval [CI], 1.73 to 12.22) compared with carriers of the Glu298 allele. After a multivariate analysis, carriage of the "Asp298-786C-4b" haplotype was also associated with increased risk of preeclampsia (OR, 2.11 [95% CI, 1.33 to 3.34]) compared with carriers of the "Glu298-786T-4b" haplotype. The eNOS Glu298Asp polymorphism and the Asp298-786C-4b haplotype are risk factors for preeclampsia.