Polimorfismo de proteína 5, 10-metilentetrahidrofolatoreductasa en población venezolana / Polymorphisms proteína 5, 10-metilentetrahidrofolatoreductasa in venezuelan people

El folato es un miembro del grupo de la vitamina B y está relacionado con enfermedades crónicas como anemia megaloblástica, enfermedad cardiovascular, cáncer, disfunción cognitiva y riesgo de defectos del tubo neural. La proteína 5,10-metilentetrahidrofolato reductasa (MTHFR) juega un papel clave en el metabolismo del folato mediante la síntesis de nucleótidos y reacciones de metilación. El gen MTHFR se encuentra en el cromosoma 1 (1p36.3), y se han descrito dos alelos comunes, el alelo C677T (termolábil) y el alelo A1298C.El objetivo de este estudio es evaluar la distribución de los polimorfismos genéticos en MTHFR C677T y A1298C en la población venezolana. METODOS: estudio de tipo transversal, descriptivo, experimental y correlacional Las muestras de sangre se colectaron en 314 donantes no emparentados y sanos de la población. Los polimorfismos de un solo nucleótido(SNP) MTHFR 677C>T y 1298A>C se analizaron mediante polimorfismo de longitud de fragmento de restricción de reacción en cadena de polimerasa (PCR-RFLP). El desequilibrio de ligamiento (LD) entre pares de SNP se calculó mediante la prueba X. usando Prism 5 (GraphPad software, Inc). RESULTADOS: Encontramos mayor frecuencia genotípica de heterocigotos para el polimorfismo MTHFR C677T en la población general venezolana, con excepción del grupo caucásico. El polimorfismo MTHFR A1298C en el 70%de la población de estudio es homocigoto de tipo salvaje, encontrándose una baja frecuencia de homocigoto mutado. CONCLUSIONES: Se encontraron diferencias significativas entre grupos étnicos, destacando la importancia del genotipado racial de estos polimorfismos en la población venezolana(AU)

Folate is a member of the vitamin B and it has also been indicated that may be related to chronic diseases such as megaloblastic anemia, cardiovascular disease, cognitive dysfunction and risk of neural tube. Methylenetetrahydro folatereductase (MTHFR) is a key enzyme of folate pathway by nucleotide synthesis and methylation reactions. Several polymorphisms were reported in MTHFR gene but C677Tand A1298 polymorphism are most studied and these have been reported to be risk factor for several diseases/disorders. The present study was designed to determine the frequency of MTHFR polymorphisms in Venezuelan healthy population. METHODS: The blood samples were collected from 314 unrelated and healthy donors from population. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through the .. test using Prism 5 (GraphPad sftoware, Inc). RESULTS: We find higher genotypic frequency of heterozygotes for the MTHFR C677T polymorphism in the Venezuelan general population, with the exception of the Caucasian group. MTHFR A1298C polymorphism in 70%of the study population is homozygous wild type, finding alow frequency of homozygous mutated. CONCLUSIONS: Significant differences between ethnic groups were found,highlighting the importance of racial genotyping of these polymorphisms in the Venezuelan population(AU)

Predisposing role of heterozygote MTHFR A1298C mutation in venous thrombosis in a pregnant patient: A case report.

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis (VT). Several genetic mechanisms have been investigated for their possible relationship with VT. Methyl tetrahydrofolate reductase gene polymorphisms are frequently in the MTHFR gene, which leads to a C to T change at position 677, has been suggested to alter the thrombohemostasis process and thrombophilia. Also, it has been found that MTHFR C1298C or MTHFR A1298C have no effect on the risk of VT. Herein, we describe deep VT (DVT) secondary to heterozygous MTHFR A1298C mutation in pregnant woman.

A Case-control Study on the Relationship between Methylenetetrahydrofolate Reductase C677T, A1298C and G1793A Polymorphism and the Risk of Stomach Cancer

PURPOSE: The methylenetetrahydrofolate reductase (MTHFR) play a central role in converting folate to methyl donor for DNA methylation. Genetic variation in folate metabolism are believed to contribute to the risk of acute lymphoblastic leukemia, colon, esophageal and stomach cancer, as well as cardiovascular and cerebrovascular disease. Generally, low folate level is known that it is associated with gastrointestinal neoplasm. Three common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (C677T/Ala222Val, A1298C/Glu428Ala and G1793A/Arg594Glu) has been described in MTHFR. We studied the relation of MTHFR C677T, A1298C and G1793A polymorphisms derived from stomach cancers and a control group in Korean people. METHODS: We performed a case-control study to examine the relationship between MTHFR C677, A1298C and G1793A polymorphism and the risk of stomach cancer. 124 individuals with stomach cancer and 288 healthy persons were analyzed. Blood sampling of each groups were performed, PCR-RFLP analyzed, as a results, MTHFR polymorphism genotypes of 677C/C, 677C/T, 677T/T, 1298AA, 1298AC, 1298CC, 1793GG, 1793GA and 1793AA were obtained. RESULTS: The genotype frequency of MTHFR C677T polymorphisms were 23.4% (CC), 51.6% (CT), 25.0% (TT), 76.6% (CT+TT) in case patients and 39.2% (CC), 36.8% (CT), 24.0% (TT), 60.8% (CT+TT) in control groups. The genotype frequency of MTHFR A1298C polymorphisms were 38.7% (AA), 54.0% (AC), 7.3% (CC), 61.3% (AC+CC) in case patients and 55.6% (AA), 40.3% (AC), 4.2% (CC), 44.4% (AC+CC) in control groups. The genotype frequency of MTHFR G1793A polymorphisms were 82.3% (GG), 16.9% (GA), 0.8% (AA), 17.7% (GA+AA) in case patients and 85.8% (GG), 11.8% (GA), 2.4% (AA), 14.2% (GA+AA) in control groups. 677TT and 677CT genotype was associated with a significantly increased risk for gastric cancer (adjusted OR=2.15, 95% confidence interval 1.16~3.95 in TT, adjusted OR=2.49, 95% CI 1.47~4.20 in CT) than the 677CC genotype, and 1298CC and 1298 AC genotype also was associated with a significantly increased risk for stomach cancer (adjusted OR=2.87, 95% CI 1.10~|7.49 in CC, adjusted OR= 2.07, 95% CI 1.31~3.26 in AC). But 1793AA and 1793GA genotypes were not association with a significantly increased risk for stomach cancer (adjusted OR=0.29, 95% CI 0.03~|2.47 in AA, adjusted OR=1.55, 95% CI 0.84~2.86 in GA) CONCLUSION: MTHFR C677T and A1298C polymorphism may influence stomach cancer, but MTHFR G1793A polymorphism need careful interpretation and confirmation in larger studies.

Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms in Colorectal Cancer

PURPOSE: Recently, the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, pre-mature vascular disease, neural tube defects, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancers and gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism, and influences DNA synthesis and DNA methylation. Generally, a low folate level is known to be associated with gastrointestinal neoplasms. Also, the amino- acid-changing and enzyme-activity-reducing nucleotide polymorphism (677C-->T/Ala222Val) has been described in the MTHFR polymorphism and it brings about low enzyme activity, which may reduce DNA methylation and uracil misincorporation into DNA. These processes may be critical for the oncogenic transformation of human cells. Two common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (677C T/Ala222Val and 1298A C/Glu428Ala) have been described in MTHFR. We investigated the relation between the MTHFR C677T and A1298C polymorphisms derived from colorectal cancers and from controls in the Korean population. METHODS: One hundred forty-eight (148) individuals with colorectal cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed by using a PCR- RFLP analysis, and MTHFR polymorphism genotypes of 677C/C, 677C/T, 677T/T, 1298AA, 1298AC, and 1298CC were obtained. RESULTS: The genotype frequencies of MTHFR C677T polymorphisms were 25.0% (CC), 48.0% (CT), 27.0% (TT), and 75.0% (CT+TT), respectively, in case patients and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in controls. The genotype frequencies of MTHFR A1298C polymorphisms were 56.1% (AA), 372% (AC), 6.8% (CC), and 43.9% (AC+CC), respectively, in case patients and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in controls. The 677TT and the 677CT genotypes were associated with significantly increased risks for colorectal cancer (adjusted OR=1.77 and 95% CI=1.02~3.04 in TT; adjusted OR=2.07 and 95% CI=1.28~3.35 in CT) than was the 677CC, genotype but the the 1298CC and 1298 AC genotypes were not associated with significantly increased risks for colorectal cancer (adjusted OR=1.75 and 95% CI= 0.71~4.26 in CC; adjusted OR=0.95 and 95% CI=0.62~1.45 in AC). CONCLUSIONS: The MTHFR C677T polymorphism may be influenced by colorectal cancer, but the role of the MTHFR A1298C polymorphism needs careful interpretation and confirmation in larger studies.