title: Association of MDR1 gene polymorphism (G2677T) with imatinib response in Egyptian chronic myeloid leukemia patients.
abstract: BACKGROUND
  Despite the excellent efficacy results of imatinib treatment in CML patients, resistance to imatinib has emerged as a significant problem. Genetic variations in genes involved in drug transportation might influence the pharmacokinetic and metabolism of imatinib. The genotype of a patient is increasingly recognized in influencing the response to the treatment.
  
  
  OBJECTIVE
  To investigate the genotype frequencies of single nucleotide polymorphisms (SNPs) G2677T in CML patients undergoing imatinib treatment to determine whether different genotype pattern of these SNPs have any influence in mediating response to imatinib.
  
  
  METHODS
  A total of 96 CML and 90 control samples were analyzed for the human multidrug resistance gene 1 (MDR1) gene polymorphism (G2677T) using polymerase chain reaction-restriction fragment length polymorphism technique.
  
  
  RESULTS
  Genotype distribution revealed a significant lower frequency of TT genotype in CML patients and non-significant difference in the GG, GT genotype frequencies between patients and controls (P = 0.004, 0.138, 0.210, respectively). GG genotype was significantly higher in chronic phase (P = 0.046), while GT genotype was significantly higher in Blastic crisis phase (P = 0.002). There was a significant difference in genotype frequency of G2677T among patients showing response and resistance to imatinib in chronic phase (P = 0.02). TT genotype was associated with complete hematological response (P = 0.01), complete cytogenetic response (P < 0.001), and better molecular response with a significant association (P < 0.001). GT genotype was associated with partial hematological response (P = 0.01) and minor cytogenetic response (P < 0.001). Optimal and suboptimal responses were observed for patients with TT genotype (P = 0.003). Failure of drug response was associated with GT genotype (P = 0.02); however, GG had no association with drug response. Multivariate analysis considered GT genotype as independent risk factor for resistance (P = 0.037), while TT genotype as protective factor against resistance to imatinib (P = 0.008).
  
  
  CONCLUSIONS
  Determination of MDR1 polymorphisms (G2677T) might be useful in response prediction to therapy with imatinib in patients with CML.
authors.forename: Doaa M
authors.initials: DM
authors.lastname: Elghannam
authors.forename: Lamia
authors.initials: L
authors.lastname: Ibrahim
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ebrahim
authors.forename: Emad
authors.initials: E
authors.lastname: Azmy
authors.forename: Hazem
authors.initials: H
authors.lastname: Hakem
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D001549:Benzamides / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukemia; Imatinib; MDR1 gene; Polymorphism