Asset Details
Do you wish to reserve the book?
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
Do you wish to request the book?
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
2014
Overview
Purpose
To investigate the correlation between common genetic polymorphisms of folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), and methylenetetrahydrofolate reductase (MTHFR) and serum levels of methotrexate (MTX) in Chinese children with acute lymphoblastic leukemia (ALL).
Methods
Ninety-one children with ALL who received high-dose MTX were recruited. The polymorphisms
FPGS
(rs1544105 G>A),
GGH
(rs3758149 C>T), and
MTHFR
(rs1801133 C>T) were genotyped through polymerase chain reaction-restriction fragment length polymorphism analysis. Serum MTX was measured by fluorescence polarization immunoassay. The association between targeted polymorphisms and MTX concentration-to-dose (C/D) ratios was assessed, and between targeted polymorphisms and the percent of MTX above the therapeutic threshold (40 µmol/L).
Results
The minor allele frequencies of rs1544105 G (34.1 %), rs3758149 T (19.2 %), and rs1801133 C (48.4 %) observed in our population were significantly lower than those reported for European populations (64.2, 30.8, and 69.0 %, respectively). The association between the
GGH
rs3758149 polymorphism and MTX C/D was gender-specific; in girls, the MTX C/D at 24 h of
GGH
rs3758149 CC carriers (12.09 μmol/L per g/m
2
) was significantly lower than that of CT or TT carriers (16.80 μmol/L per g/m
2
). The percent of serum MTX above the therapeutic threshold in
GGH
rs3758149 CC carriers (18.3 %) was significantly lower than that of CT and TT carriers (38.7 %). The MTX C/D ratios at 24 h and the percent of MTX >40 µmol/L for the A-T-T (three variant alleles) haplotype were significantly higher than those for other haplotypes combined (
P
< 0.05).
Conclusions
These data indicate that
FPGS
rs1544105,
GGH
rs3758149, and
MTHFR
rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
/ Asian Continental Ancestry Group - genetics
/ Biological and medical sciences
/ Child
/ Female
/ gamma-Glutamyl Hydrolase - genetics
/ Hematologic and hematopoietic diseases
/ Humans
/ Infant
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Male
/ Medicine
/ Methotrexate - administration & dosage
/ Methylenetetrahydrofolate Reductase (NADPH2) - genetics
/ Oncology
/ Peptide Synthases - genetics
/ Pharmacology. Drug treatments
/ Polymorphism, Restriction Fragment Length
/ Polymorphism, Single Nucleotide - genetics
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
