Demethylation of the promoter region of GPX3 in a newborn with classical phenylketonuria

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• 作者：Chike Bellarmine Item ; ^{bellarmine.item@meduniwien.ac.at} ; Sharmane Escueta ; Andrea Schanzer ; Somayeh Farhadi ; Thomas Metz ; Maximilian Zeyda ; Dorothea Mö ; slinger ; Susanne Greber-Platzer ; Vassiliki Konstantopoulou
• 关键词：GPX3 ; glutathione peroxidase 3 ; CpG ; cytosine phosphodiester bond guanine ; PKU ; phenylketonuria ; phe ; phenylalanine
• 刊名：Clinical Biochemistry
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：3
• 页码：159-161
• 全文大小：358 K
• 卷排序：50

文摘

Phenylketonuria (PKU) is characterized by a high phenylalanine (phe) in plasma and oxidative stress. However, the monitoring of oxidative stress in newborns with PKU using the activity levels of antioxidant enzymes is not optimal. We investigated the possibility of monitoring an increased reactive oxygen species (ROS) production using DNA methylation changes of an oxidative stress response element in the promoter region of an enzymatic antioxidant gene.Design and methodsUsing DNA extracted from blood leukocytes, the cytosine phosphodiester bond guanine positions of an overlapping CCAAT box/metal response element (CGATTGGCTG) of the glutathione peroxidase 3 promoter activated by oxidative stimuli and expressed in plasma were analysed for methylation changes in 20 newborns with hyperphenylalaninemia and 20 healthy controls.ResultsA demethylated allele was detected in a PKU patient at a phe level of 465 μmol/L on day 2 after birth, but not in other patients (phe < 465 μmol/L, ≥ day 2 after birth; phe > 465 μmol/L, ≥ day 3 after birth) and healthy controls (phe < 465 μmol/L, ≥ day 2 after birth).ConclusionsThe detection of the demethylated allele could be time and phe concentration dependent. The demethylated allele is suggested as an early epigenetic marker for an extracellular monitoring of an increased ROS production in newborns with PKU.