Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia.
Genetic variations in the polymorphic tandem repeat sequence of the enhancer region of the thymidylate synthase promoter (TSER), as well as in methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, influence methotrexate sensitivity. We studied these polymorphisms in children with acute lymphoblastic leukaemia (ALL) and in subjects without malignancy in Indonesia and Holland. The frequencies of TT and CT genotypes were two-fold higher in Dutch children. The TSER 3R/3R repeat was three-fold more frequent in the Indonesian children, while the 2R/2R repeat was only 1% compared to 21% in the Dutch children. No differences of these polymorphisms were found between ALL cells and normal blood cells, indicating an ethnic rather than leukemic origin. These results may have implications for treatment of Indonesian children with ALL.
Giovannetti
Elisa
E
Department of Medical Oncology, VU Institute for Cancer and Immunology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Ugrasena
Dewa G
DG
Supriyadi
Eddy
E
Vroling
Laura
L
Azzarello
Antonino
A
de Lange
Desiree
D
Peters
Godefridus J
GJ
Veerman
Anjo J P
AJ
Cloos
Jacqueline
J
D000328:Adult; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007214:Indonesia; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009426:Netherlands; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020080:Tandem Repeat Sequences; D013940:Thymidylate Synthase / Q000235:genetics*
D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D008727:Methotrexate