1,721,212 research outputs found
GENE-NUTRIENT INTERACTIONS AND EPIGENETICS. BIOCHEMICAL BASES OF THE ROLE OF PLASMA AND RED BLOOD CELL FOLATE, THE MTHFR C677T POLYMORPHISM AND GENOMIC DNA METHYLATION.
No full textLa metilazione del DNA, una caratteristica epigenetica essenziale del DNA che modula l'espressione genica e l'integrità del genoma, è catalizzata da metiltrasferasi che utilizzano la S-adenosilmetionina (SAM) quale donatore universale di gruppi metilici. L'enzima metilenetetraidrofolato reduttasi (MTHFR) catalizza la sintesi del 5-metiltetraidrofolato (5-methylTHF), il donatore di gruppi metilici per la sintesi di metionina dall'omocisteina e precursore della SAM. Nel presente studio si è voluto determinare l'effetto dello status dei folati sulla metilazione genomica del DNA con particolare enfasi sul ruolo di una possibile interazione genetico-nutrizionale con la mutazione comune a carico del gene MTHFR. Un nuovo metodo ad elevata sensibilità e specificità per l'analisi delle basi nucleotidiche, basato su tecnologia LC/ESI-MS, è stato da noi inventato e messo a punto per determinare la metilazione genomica del DNA da materiale nucleico isolato da cellule mononucleate da sangue periferico di 105 soggetti omozigoti per la mutazione comune del gene MTHFR (T/T) e 187 soggetti wild-type (C/C) per il medesimo polimorfismo genico. I risultati del presente lavoro hanno dimostrato che la metilazine genomica del DNA correla in modo diretto con lo status dei folati (P<0.01). I genotipi T/T hanno ridotti livelli di metilazione del DNA rispetto ai soggetti wild-type (C/C) (32.23 vs.62.24 ng 5-methylcytosine/mg DNA, P<0.0001). Tuttavia, solamente i soggetti con genotipo T/T con bassi livelli di folatemia rendevano conto dei ridotti livelli di metilazione genomica del DNA (P<0.0001). Dato particolarmente innovativo ed interessante è la scoperta che nei soggetti portatori del genotipo T/T la metilazione del DNA correlava con la porzione metilata dei folati eritrocitari (RBC folates) ed era inversamente proporzionale con la porzione formilata dei folati eritrocitari (P<0.03)che è noto essere presente solamente nei soggetti portatori del genotipo mutante MTHFR T/T. Questi risultati indiacano pertanto che il polimorfismo MTHFR C677T influenzano il principale meccanismo epigenetico del DNA attraverso una interazione genetico-nutrizionale con lo status dei folati.DNA methylation, an essential epigenetic feature of DNA that modulates gene expression and genomic integrity, is catalyzed by methyltransferases that utilize the universal methyl donor S-adenosyl-L-methionine (SAM). Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), the methyl donor for synthesis of methionine from homocysteine and precursor of SAM. In the present study we sought to determine the effect of folate status on genomic DNA methylation with an emphasis on the interaction with the common C677T mutation in the MTHFR gene. A newly developed sensitive and selective LC/ESI-MS method for the analysis of nucleotide bases was used to assess genomic DNA methylation in peripheral blood mononuclear cell DNA from 105 subjects homozygous for this mutation (T/T) and 187 homozygous for the wild-type (C/C) genotype. The results show that genomic DNA methylation directly correlates with folate status (P<0.01). T/T genotypes had a diminished level of DNA methylation compared to those with the C/C wild-type (32.23 vs.62.24 ng 5-methylcytosine/mg DNA, P<0.0001). Only the T/T subjects with low levels of folate, however, accounted for the diminished DNA methylation (P<0.0001). In T/T subjects DNA methylation status correlated with the methylated proportion of red blood cell folate (RBC) and was inversely related to the formylated proportion of RBC folates (P<0.03) that is known to be solely represented in those individuals. These results indicate that the MTHFR C677T polymorphism influences DNA methylation status through an interaction with folate status
Interactions between folate and methylentetrahydrofolate reductase (MTHFR) gene in cancer.
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Nutrient-gene interactions in cancer
No full textIn the era of ancient Greek medicine Hippocrates postulated that an imbalance of humors (blood, phlegm, black bile and yellow bile) resulted in disease and Galen introduced four basic temperaments of human reflecting the humors (the sanguine, buoyant type; the phlegmatic, sluggish type; the choleric, quick-tempered type; and the melancholic, dejected type). Thereafter both Western and Oriental medicine have tried to classify human into different types to increase the treatment efficacy and have believed that these types affect physiology, pathology, diagnosis, treatment and prognosis of diseases. These old classifications were based on physical shapes or tempers (phenotypic expression) but nowadays we are trying to classify human as genotypes to predict the disease risk as well as to develop better strategies for the prevention and treatment of disease.
Early researches regarding the relationship between diet and cancer were based on the idea that the cancer is caused by an overexposure to a specific diet. With a more clear knowledge gained in recent years that cancer is a genetic disease, as shown by molecular aberrations in many genes, most of the studies have focused more specifically on the effect of particular nutrients on the expression of genes related to carcinogenesis. Most recently, the complete mapping of the human genome and sophisticated molecular technologies have accelerated researches on the relationship between nutrients and genes. Consequently compelling evidences from epidemiological and experimental observations have suggested that the risk of a certain cancer is different from each genotype of critical genes and have supported that the interaction between nutrient and gene is one of the most important mechanisms by which nutrients modulate carcinogenesis.
This book specifically focuses on the interaction between nutrients and genes in cancer, which, we believe, highlights that nutrient has not just one simple function in cancer development but, more notably, that nutrition is one of the most important factors, which serves as a modulator for cancer development through the interaction with specific genes. A deeper understanding in such relationship has also contributed to find a new strategy for cancer chemoprevention with nutrition. In this book we have endeavored to provide a comprehensive and systematic review of the latest information regarding the role of nutrients and genes interactions on cancer development, with the aim of providing also specific examples of well-known interactions between nutrients and genes with a defined pathogenetic role in clinical manifestations of different cancer diseases.
The first part of the book includes chapters on the basic elements of biology and pathobiology of gene-nutrient interactions with a focus on mechanisms and biomarkers. Thereafter each chapter describes in detail regarding specific gene-nutrients interactions which are currently available in many different types of cancer. Each chapter also describes the currently available methodologies to evaluate each nutrient and gene interaction. This section has been thought both for basic-science investigators as well as for clinicians who manage cancer patients with the intent of giving useful tools which face the clinical implications of the gene-nutrient interaction field in medical nutrition and oncology. In contemporary medicine, moreover, not only oncology specialists meet the need of a continuing appreciation of this emerging field, but also many others among specialists and scientists are confronted with this emerging field of nutrition and genetics interactions. The last chapter of the book emphasizes upcoming directions and implications of the significance of fostering future researches as well as perceiving new prospective in this specific and rapidly growing theme of medical science.
We would like to thank our esteemed authors, who are among the leading authorities in the field, for their marvelous contribution to each chapter as well as our admired readers for their dedication, present and future, to this unique and fascinating field, ‘the interaction of nutrients and genes in cancer’. We also would like to thank the CRC press to provide us an arena to discuss about a valuable scientific topic and most of all we give thanks to God to show us his secret, the gene-nutrient interaction, for the health of all mankind
Effects of the interaction between folate status and the MTHFR 677C/T polymorphism on genomic DNA methylation
No full textEffects of the interaction between folate status and MTHFR 677C-T polymorphism on genomic DNA methylation
No full textIs it worthwhile to try different coenzymatic forms of folate in future chemoprevention trials?
No full textDiscordance and shortcomings of aldosterone suppression tests in primary aldosteronism
No full textAldosterone suppression tests in primary aldosteronism may show several variations and shortcoming
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