Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer.

Folate, vitamin B2, vitamin B6, vitamin B12, choline, and betaine are nutrients involved in the 1-carbon cycle that can alter the levels of DNA methylation and influence genesis and/or tumor progression. Thus, the objective of this study was to evaluate the association of folate and vitamins involved in the 1-carbon cycle and MTHFR polymorphisms in global DNA methylation in patients with colorectal cancer gene. The study included 189 patients with colorectal adenocarcinoma answering a clinical evaluation questionnaire and the Food Frequency Questionnaire (FFQ) validated for patients with colon and rectal cancer. Blood samples were collected for evaluation of MTHFR gene polymorphisms in global DNA methylation in blood and in tumor. The values for serum folate were positively correlated with the equivalent total dietary folate (total DFE) (rho = 0.51, p = 0.03) and global DNA methylation (rho = 0.20, p = 0.03). Individuals aged over 61 years (p = 0.01) in clinicopathological staging III and IV (p = 0.01) and with + heterozygous mutated homozygous genotypes for the MTHFR A1298C gene had higher levels of global DNA methylation (p = 0.04). The association between dietary intake of folate, serum folate, and tumor stage were predictive of global DNA methylation in patients' blood. The levels of serum folate, the dietary folate and the status of DNA methylation can influence clinicopathological staging.

[Central nervous system malformations and the presence of the MTHFR-C677T mutation in fetal blood]. / Malformações do sistema nervoso central e a presença da mutação C677T-MTHFR no sangue fetal.

PURPOSE: To evaluate the association between central nervous system (CNS) malformations and the C677T-MTHFR mutation in fetal blood. METHODS: A case-control study was conducted to compare the MTHFR-C677T mutation detected in 78 fetuses with CNS malformations and with 100 morphologically normal fetuses. Genomic DNA was extracted and purified from fetal blood using the Wizard® Genomic DNA Purification Kit (Promega Corp., Madison, WI, USA) according to manufacturer's protocol. The polymerase chain reaction (PCR) was used to assay the thermolabile MTHFR-C677T mutation. The γ² and the Fisher's exact tests were used for descriptive analysis and the Wilcoxon test was used for univariate analysis. Logistic regression analysis was performed to identify which variables were predictors of CNS malformation. RESULTS: Cases and controls were similar regarding maternal characteristics such as age and number of deliveries and abortions. The MTHFR-C677T mutation was detected in 20 cases (25.6%) and in 6 controls in its heterozygous form (OR 10.3; 95%CI 3.3-32.2) and in 6 cases (7.7%) and in 1 control in its homozygous form (OR 12.3; 95%CI 1.3-111.1), and the differences were statistically significant. CONCLUSION: The presence of the MTHFR-C677T mutation in fetal blood was consistent with a higher risk of CNS malformations, both in the heterozygous and homozygous forms.

Relación entre el polimorfismo C677T de la metilentetrahidrofolato reductasa y la aterosclerosis / Relation between polymorphism C677T of the methylenetetrahydrofolate reductase and atherosclerosis

La hiperhomocisteinemia ha sido considerada un importante factor de riesgo para varias enfermedades vasculares, así como la mutación C677T de la metilentetrahidrofolato reductasa (MTHFR), que causa la formación de una enzima termolábil y con actividad disminuida. El objetivo de este trabajo fue detectar la prevalencia de este polimorfismo en una población de pacientes que padecían enfermedad arterial coronaria (EAC) precoz y correlacionar los genotipos encontrados con el perfil clínico de los mismos individuos. Para ello, fueron citados 112 pacientes sometidos a cateterismo en una clínica particular de Florianópolis (SC Brasil) y a examen clínico y extracción sanguínea por punción venosa. Se aisló el ADN y se determinó el genotipo para el polimorfismo C677T a través del método de polimorfismo de fragmentos de restricción (RFLP). La frecuencia del alelo alterado T fue del 23% en la población portadora de EAC precoz y del 25% en el grupo control. No se observaron diferencias significativas entre los grupos con respecto a la presencia de ninguno de los factores de riesgo analizados. Entre los pacientes con resultado de cateterismo alterado, la historia familiar previa de eventos vasculares estuvo presente en el 91,9% de los pacientes heterocigotos, contra un 72,2% en los homocigotos normales. Los resultados obtenidos permiten concluir que, en la población estudiada, el polimorfismo C677T parece no representar factor de riesgo aislado para la aterosclerosis, mientras que, en presencia de historia familiar, contribuye al desarrollo de enfermedades vasculares.

Hyperhomocysteinemia has been considered an important risk factor for some vascular diseases, as well as a C677T mutation of the methylenete-trahydrofolate reductase (MTHFR), that causes formation of a thermolabile enzyme with reduced activity. The objective of this work was to detect the prevalence of this polymorphism in a population of early coronan/ artery disease patients and to correlate the genotypes found with the el i nica I profile of the same individuáis. To this aim, 112 patients that had undergone cardiac catheterization in a prívate hospital in Florianópolis (SC Brazil) were recruited and submitted to clinical examination and blood test. DNA was isolated and the genotype for polymorphism C677T determined by the RFLP (restriction fragment length polymorphism) method. The frequeney of T-alleles was 23% in the carrier population and 25% in the control group. No significant differences between thegroups regarding the presence of any of the analyzed risk factors were observed. In the group of patients with resulting modified catheterization, previous family history of vascular disease was present in 91.9% of the heterozygote patients, against 72.2% in the normal homozygote ones. It can be concluded then that, in this population, polymorphism C677T does not seem to be an isolated risk factor for atherosclerosis, while, in presence of family history, it contributes to the development of vascular diseases.