Association of GGH Promoter Methylation Levels with Methotrexate Concentrations in Chinese Children with Acute Lymphoblastic Leukemia
Autor: | Xiao-Yan Kong, Dan Yan, Lu-Lu Sun, Shu-Mei Wang, Miao Li |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Antimetabolites Antineoplastic China Guanine Lymphoblastic Leukemia 030106 microbiology 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Asian People medicine Humans Pharmacology (medical) Child Genotyping business.industry Infant gamma-Glutamyl Hydrolase Methylation DNA Methylation Precursor Cell Lymphoblastic Leukemia-Lymphoma Methotrexate CpG site chemistry Child Preschool DNA methylation Cancer research Female business Cytosine medicine.drug |
Zdroj: | Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 40:614-622 |
ISSN: | 1875-9114 0277-0008 |
DOI: | 10.1002/phar.2430 |
Popis: | BACKGROUND It is known that γ-glutamyl hydrolase (GGH) is involved in the disposition of methotrexate (MTX), and GGH activity is regulated by DNA methylation in acute lymphoblastic leukemia (ALL) cells. The present study explores the methylation status of the GGH promoter in peripheral blood and its association with MTX levels and toxicities in Chinese children with ALL. METHODS Serum MTX concentrations were determined by fluorescence polarization immunoassay. Methylation quantification and genotyping for GGH rs3758149 and rs11545078 was performed by Sequenom MassARRAY in 50 pediatric patients with ALL. RESULTS Overall, the investigated region of the GGH promoter was in hypomethylated status. The methylation levels of cytosine phosphate guanine (CpG)_7, CpG_12, CpG_17, and CpG_20 were significantly higher in patients with B-cell ALL than other immunotypes (p |
Databáze: | OpenAIRE |
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