›› 2011, Vol. 31 ›› Issue (1): 47-.doi: 10.3969/j.issn.1674-8115.2011.01.011

• Original article (Clinical research) • Previous Articles     Next Articles

Relationship between RAC2 genetic polymorphisms and daunorubicin-induced cardiotoxicity

HU Meng, JIANG Hui, XIA Min   

  1. Department of Hematology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, China
  • Online:2011-01-28 Published:2011-02-01
  • Supported by:

    Shanghai Shenkang Hospital Development Center Foundation, SHDC12007229

Abstract:

Objective To investigate the RAC2 genetic polymorphisms of reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in children with acute leukemia (AL), and explore the relationship between RAC2 genetic polymorphisms and daunorubicin-induced cardiotoxicity. Methods Forty-two children diagnosed as AL with conventional chemotherapy (AL group) and 25 healthy children (normal control group) were enrolled. Peripheral venous blood was obtained, and DNA was extracted. Upstream and downstream fragments of RAC2 genetic polymorphism sites were amplified by PCR, RAC2 genetic polymorphisms of rs13058338 site were detected by gene sequencing, and the distribution frequencies of RAC2 genetic polymorphisms were compared among groups. Results The total positive rate of RAC2 genetic polymorphisms was 19.4%, and there was no significant difference in distribution frequencies between AL group and normal control group (P=0.531). In AL group, there were significant differences in frequencies of RAC2 genetic polymorphisms between high level N-terminal brain natriuretic peptide (NT-proBNP)(>125 pg/mL) group (25.9%, 7/27) and normal level NT-proBNP (0-125 pg/mL) group(0, 0/15) (P=0.035), while there was no significant difference in distribution frequencies between daunomycin accumulated dose 60-120 mg/m2 group (20.0%, 5/25) and daunomycin accumulated dose >120 mg/m2 group (11.8%, 2/17)(P=0.681). In high level NT-proBNP group, there was no significant difference in NT-proBNP levels between 7 children with AT allele and 20 children with TT allele [(276.08±158.60) pg/mL vs (289.64±209.47) pg/mL, P>0.05]. Conclusion There are individual differences in RAC2 genetic polymorphisms; RAC2 genetic polymorphisms may contribute to daunorubicin-induced cardiotoxicity.

Key words: acute leukemia, daunomycin, N-terminal brain natriuretic peptide, cardiotoxicity, RAC2 genetic polymorphism