Association between glutathione S-transferase pi gene polymorphism and adverse reaction of high-dose methotrexate in children with acute lymphoblastic leukemia
10.3969/j.issn.1000-8179.20141070
- VernacularTitle:谷胱甘肽转移酶P1基因多态性与儿童ALL HD-MTX不良反应的关系
- Author:
Yanfei REN
;
Xiuli YUAN
;
Lijie YUE
;
Zeqiao ZOU
;
Cai XIE
;
Hui DING
;
Ping SONG
;
Chang LIU
- Publication Type:Journal Article
- Keywords:
glutathione S-transferase pi;
gene polymorphism;
acute lymphoblastic leukemia;
methotrexate;
toxicity
- From:
Chinese Journal of Clinical Oncology
2014;(21):1358-1362
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.
