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Influence of phenylketonuria's diet on dimethylated arginines and methylation cycle.

ABSTRACT: Phenylketonuria's (PKU) treatment based on low natural protein diet may affect homocysteine (Hcys) metabolic pathway. Hcys alteration may be related to the methylation of arginine to asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which both modify nitric oxide production. The aim of this work is to evaluate the status of Hcys formation methylation cycle and ADMA and SDMA levels in patients with PKU in order to establish a potential relationship.Forty-two early diagnosed PKU patients under dietary treatment and good adherence to their diets were enrolled in this cross-sectional study. Their nutritional and biochemical profile, as well as Hcys synthesis status, ADMA and SDMA levels were analyzed and compared with a control group of 40 healthy volunteers. ADMA and SDMA were determined by high-performance liquid chromatography system coupled to triple quadrupole mass spectrometer.In this study, 23 classic PKU, 16 moderate PKU, and 3 mild HPA were enrolled. The median age was 10 years old. Median ADMA, SDMA, and Hcys concentration levels (5.1??M [2.3-25.7], 0.35??M [0.18-0.57], 0.43??M [0.26-0.61], respectively) were lower in patients with PKU (P?

SUBMITTER: Andrade F

PROVIDER: S-EPMC5502164 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Influence of phenylketonuria's diet on dimethylated arginines and methylation cycle.

Andrade Fernando F López-Suárez Olalla O Llarena Marta M Couce María L ML Aldámiz-Echevarría Luis L

Medicine 20170701 27

Phenylketonuria's (PKU) treatment based on low natural protein diet may affect homocysteine (Hcys) metabolic pathway. Hcys alteration may be related to the methylation of arginine to asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), which both modify nitric oxide production. The aim of this work is to evaluate the status of Hcys formation methylation cycle and ADMA and SDMA levels in patients with PKU in order to establish a potential relationship.Forty-two early diagnose ...[more]

PMID: 28682891

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Project description:BackgroundMaternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers.MethodsMothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation.ResultsGenotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05).ConclusionThese findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.

Dataset Information

Influence of phenylketonuria's diet on dimethylated arginines and methylation cycle.

Publications

Influence of phenylketonuria's diet on dimethylated arginines and methylation cycle.

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