ABCB1 polymorphisms correlate with susceptibility to adult acute leukemia and response to high-dose methotrexate.
The aim of this study is to investigate the association of ABCB1 polymorphisms with susceptibility to adult acute leukemia, and the influence of ABCB1 polymorphisms on the efficacy of high-dose methotrexate (HDMTX). ABCB1 polymorphisms in 178 acute leukemia patients (case group) and 150 healthy subjects (control group) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All patients received HDMTX therapy. Correlation analysis was performed to explore the associations of ABCB1 polymorphisms with MTX concentration and efficacy of MTX therapy. All statistical analyses were conducted with SPSS 19.0 software. The frequency of TT genotype and T allele on ABCB1 3435C > T in case group were significantly higher than the control group (P < 0.05), while no statistical difference between the two groups was observed in genotypic distribution and allele frequencies of ABCB1 2677G > T/A (P > 0.05). Furthermore, 24-h MTX concentration of patients carrying TT and TA genotypes on 2677G > T/A was higher than carriers with other genotypes (P < 0.05), and 24-h MTX concentration of patients with TT and CT genotypes on 3435C > T was also apparently higher than carriers with CC genotype (P < 0.05). In addition, ABCB1 polymorphisms were connected with increased risk of liver dysfunction and infection (P < 0.05). Complete remission (CR) rate in patients carrying GG on 2677G > T/A was markedly lower than carriers with non-GG genotype (P < 0.05). ABCB1 3435C > T polymorphisms may be associated with susceptibility to acute leukemia, and ABCB1 polymorphisms might be a sensitive indicator for predicting efficacy of MTX therapy in the treatment of acute leukemia.
Department of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261035, People's Republic of China.
Chuan-Xiang
CX
Ma
Department of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261035, People's Republic of China.
Yong-Hong
YH
Sun
Department of Hematology, The Affiliated Hospital of Weifang Medical University, No.2428, Yuhe Road, Kuiwen District, Weifang, Shandong, 261035, People's Republic of China. HaiYingWang_why@yeah.net.
Hai-Ying
HY
Wang
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D008727:Methotrexate
ATP-binding cassette subfamily B member 1; Acute leukemia; Adult; Efficacy; High-dose methotrexate; Methotrexate; Serum concentration; Single nucleotide polymorphism