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
Rok vydání: 2020
Předmět:
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