Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies.

BACKGROUND: Several studies around the world support the hypothesis that genetic polymorphisms involved in folate metabolism could be related to the maternal risk for Down syndrome (DS). Most of them investigated the role of MTHFR C677T and/or A1298C polymorphisms as maternal risk factors for DS, but their results are often conflicting and still inconclusive. METHODS: We conducted a systematic review and meta-analysis to clarify the association of MTHFR C677T and/or A1298C polymorphisms with the maternal risk of DS. Our search strategy selected 42 eligible case control studies for a total of 4131 case mothers and 5452 control mothers. The Newcastle-Ottawa Scale was used to assess the methodological quality of the selected studies. To assess the confidence of statistically significant associations we applied false positive report probability test, and we performed the trial sequential analysis to minimize the type I error and random error. RESULTS: We observed significant associations between the MTHFR C677T polymorphism and maternal risk for DS for each of the genetic models investigated (dominant, recessive, codominant, and allelic contrast). Subgroup analysis by region revelated significant association in the Asian population for all the genetic models investigated. Significant associations were also found for certain genetic models in North American, South American, and Middle Eastern populations, while no association was observed in Europeans. The MTHFR A1298C polymorphism did not show any association with the maternal risk of DS, either alone or in combination with the C677T one. The results of false positive report probability to verify the confidence of a significant association suggest that the association between the MTHFR C677T polymorphism and the maternal risk for DS is noteworthy, with high confidence in Asians. CONCLUSION: The results of this meta-analysis support that the MTHFR C677T polymorphism, but not the A1298C one, is associated with the maternal risk for DS. Further studies are required to better characterize the contribution of gene-gene and gene-nutrient interactions as well as those of other regional or ethnic factors that could explain the observed different effect size in different populations.

Genotoxicity of Turnera subulata and Spondias mombin × Spondias tuberosa Extracts from Brazilian Caatinga Biome.

Medicinal plants have been used in primary healthcare since the earliest days of humankind. Turnera subulata and Spondias mombin × Spondias tuberosa are widely used in the Brazilian Northeast to treat several diseases. The aim of this study was to evaluate the genotoxic effects of the leaf extracts of these species by the somatic mutation and recombination test in the somatic cells of Drosophila melanogaster wings. The experiments were performed using standard and high-bioactivation cross and three concentrations of the test substance [aqueous extract (AET and AES) at 5.0, 10.0, and 20.0 mg/mL and ethanolic extract (EET and EES) and ethyl acetate fraction (EAFT and EAFS) at 0.625, 1.25, and 2.5 mg/mL]. Results indicated that the extracts and fractions induced spontaneous frequencies of mutant spots in both D. melanogaster crosses. Nevertheless, the highest concentrations of the tested plant chemical agents were responsible for the statistically significant genotypic effect. T. subulata and S. mombin × S. tuberosa displayed genotoxic effect under the experimental conditions. The results from this study are crucial as they indicated the deleterious and side effects, considering the indiscriminate use of the extracts of these plants for disease treatment.