One-carbon metabolism pathway genes and their non-association with the development of amyotrophic lateral sclerosis.

Although of unknown etiology, some mechanisms associated with the metabolic cycle of folate are speculated to be related to the genesis of amyotrophic lateral sclerosis (ALS). Thus, the aim of the study was to analyze the role of genetic polymorphisms rs1051266 in SLC19A1 gene and rs1805087 in MTR gene and their associations with ALS development. A case-control study was conducted with 101 individuals with ALS and 119 individuals without diagnosis of neurodegenerative diseases, from the Brazilian central population. The polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. The results showed no statistically significant differences, even when genotypes were analyzed by the dominant, recessive, codominant, and overdominant inheritance models. It was observed a statistical significance relating alcohol consumption with individuals in the case group (p = 0.01). Therefore, the need for more studies to evaluate the influence of genetic variants is highlighted, seeking to provide information on the etiopathogenesis of ALS.

GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: A genetic association study in Brazilian patients.

BACKGROUND: The role of oxidative stress in schizophrenia has been demonstrated, particularly in subjects with treatment-resistant schizophrenia (TRS). In such patients, the decreased levels of antioxidants in conjunction with the increased generation of reactive oxygen species in the brain exposes the neurons to a higher risk of damage. METHODS AND FINDINGS: We evaluated the association of deletion polymorphisms of two genes of the antioxidant Glutathione S-Transferase family, GSTT1 and GSTM1, with susceptibility to TRS. A total of 54 TRS patients (mean age 38.7 years) and 78 healthy control subjects (mean age 39.0 years) were enrolled in this study. The subjects were matched by sex, age, and smoking and alcohol consumption habits. In the case group, the frequencies of GSTT1-null and GSTM1-null genotypes were 24.1 and 51.9%, respectively, whereas for the control group, the frequencies were 12.8 and 46.2%, respectively. Analysis performed with respect to the risk of developing TRS associated with the GSTT1 and GSTM1 deletion polymorphisms, resulted in odds ratio (OR) values of 2.1 and 1.2, respectively. However, the association was not found to be significant (p = 0.1229 and p = 0.5916, respectively). The analysis performed with respect to the combined genotypes of GSTT1 and GSTM1 revealed that the double-null genotype confers a 4.6-fold increased risk of developing TRS (p = 0.0412). CONCLUSION: The results of the present study indicate that a combination of GST deficiencies may play a role in enhanced susceptibility to TRS, and the present genotype of one of these genes may buffer the deficiency caused by the lack (null genotype) of the other. The results suggest that combined deletion polymorphisms of GSTT1 and GSTM1 can have implications in the prediction of the clinical course of the disease.

Exequibility of differential gene expression analysis by DDRT-PCR in murine bone marrow cells / Exequibilidade do DDRT-PCR para análise da expressão gênica diferencial em células de medula óssea murina

Model of study: Experimental study. Introduction: Recently, stem cell research has generated great interest due to its applicability in regenerative medicine. Bone marrow is considered the most important source of adult stem cells and the establishment of new methods towards gene expression analysis regarding stem cells has become necessary. Thus Differential Display Reverse Transcription Polymerase Chain Reaction (DDRT-PCR) may be an accessible tool to investigate small differences in the gene expression of different stem cells in distinct situations. Aim: In the present study, we investigated the exequibility of DDRT-PCR to identify differences in global gene expression of mice bone marrow cells under two conditions. Methods: First, bone marrow cells were isolated fresh and a part was cultivated during one week without medium replacement. Afterwards, both bone marrow cells (fresh and cultivated) were submitted to gene expression analyses by DDRT-PCR...

Modelo do estudo: Estudo Experimental. Introdução: Atualmente a pesquisa com células-tronco tem gerado grande interesse devido a sua aplicabilidade no campo na medicina regenerativa. A medula óssea é considerada a maior fonte de células-tronco adultas e o estabelecimento de novos métodos para a análise da expressão gênica torna-se estritamente necessário. Desse modo, o "Differential Display Reverse Transcription Polymerase Chain Reaction (DDRT-PCR)", pode ser uma ferramenta acessível para investigação de pequenas diferenças no nível de expressão gênica em diferentes tipos celulares, sob distintas condições. Objetivo: Neste presente trabalho nós investigamos a exequibilidade do DDRT-PCR na identificação de diferenças no nível de expressão gênica global em células da medula óssea de camundongos sob duas condições. Métodos: Primeiramente, a medula óssea foi isolada frescamente e uma secunda parte foi cultivada por uma semana sem troca de meio. Posteriormente, as células da medula (fresca e cultivada) foram submetidas a análise da expressão gênica, seguindo a metodologia de DDRT-PCR...