Relationships of ABC subfamily G member 2 gene polymorphism with therapeutic effect of high-dose methotrexate and renal function injury in children with pediatric acute lymphoblastic leukemia

GE Yirong; RAO Mei; BI Jing; TAN Sihai; HAN Bin

doi:10.7619/jcmp.20215054

Journal of Clinical Medicine in Practice > 2022 > 26(9): 40-44. > DOI: 10.7619/jcmp.20215054

GE Yirong, RAO Mei, BI Jing, TAN Sihai, HAN Bin. Relationships of ABC subfamily G member 2 gene polymorphism with therapeutic effect of high-dose methotrexate and renal function injury in children with pediatric acute lymphoblastic leukemia[J]. Journal of Clinical Medicine in Practice, 2022, 26(9): 40-44. DOI: 10.7619/jcmp.20215054

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Relationships of ABC subfamily G member 2 gene polymorphism with therapeutic effect of high-dose methotrexate and renal function injury in children with pediatric acute lymphoblastic leukemia

Department of Pediatric Hematology, Digestion and Nephrology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, 445000

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Received Date: December 21, 2021
Available Online: May 09, 2022
Published Date: May 14, 2022

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Abstract

Abstract

Objective To investigate the relationships of ABC subfamily G member 2 ( ABCG2) gene polymorphism with therapeutic effect of high-dose methotrexate (HDMTX) and renal function injury in children with pediatric acute lymphoblastic leukemia (ALL).
Methods A total of 167 children with ALL from January 2011 to January 2019 were selected as research objects. All children were genotyped for ABCG2 (rs2231137, rs2231142) polymorphism. Multivariate regression model was used to analyze the effects of genetic polymorphism on the occurrence of HDMTX-related toxicity and event-free survival (EFS) of children.
Results The genotypes determined by the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method were located in rs2231137 sites including 87 cases with GG wild type (52.1%), 52 cases with AG heterozygous type (31.1%), and 28 cases with AA homozygous type (16.8%) and rs2231142 sites including 115 cases with CC wild type (68.9%), 38 cases with CT heterozygous type (22.8%), and 14 cases with TT homozygous type (8.3%). The risk of renal function injury in rs2231142 with (CT+TT) genotype was 14.14 times higher than that with CC wild type (OR=14.14, 95%CI, 1.26 to 42.37, P=0.032). The 72-month EFS of the individuals with (AG+AA) genotypes in rs2231137 was worse than that with the GG genotype, and the 72-month EFS of the rs2231142 with (CT+TT) genotypes was worse than that with the CC genotype, but the differences were not statistically significant (P>0.05).
Conclusion ABCG2 rs2231142 gene polymorphism in children with ALL is associated with renal function injury in the toxic and side effects of HDMTX chemotherapy, which may help to guide and optimize MTX treatment in children with ALL.
- ABC subfamily G member 2,
- methotrexate,
- acute lymphoblastic leukemia,
- polymorphism,
- renal function

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Relationships of ABC subfamily G member 2 gene polymorphism with therapeutic effect of high-dose methotrexate and renal function injury in children with pediatric acute lymphoblastic leukemia