Abstract:
Objective To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxicities 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, heterozygous 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 gastrointestinal toxicity (OR=0.125, 95% CI=0.02-0.78, P=0.026).
Conclusion GSTP1 rs1695(A313G)/rs4891(T555C) gene polymorphism is associated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and intermediate-risk ALL children who receive high-dose methotrexate.