title: Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.
abstract: BACKGROUND
  This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML).
  
  
  METHODS
  In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy.
  
  
  RESULTS
  The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR.
  
  
  CONCLUSIONS
  The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.
authors.affiliation: Department of Biomedical Science and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu 700-721, Republic of Korea.
authors.forename: S J
authors.initials: SJ
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authors.forename: S K
authors.initials: SK
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authors.forename: J H
authors.initials: JH
authors.lastname: Moon
authors.forename: S-J
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authors.forename: B S
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authors.forename: Y D
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authors.lastname: Joo
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authors.forename: D H
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authors.forename: S S
authors.initials: SS
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authors.forename: H G
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authors.lastname: Lee
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authors.lastname: Min
authors.forename: J W
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authors.initials: MK
authors.lastname: Kim
authors.forename: H
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authors.lastname: Kim
authors.forename: M R
authors.initials: MR
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: C S
authors.initials: CS
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: E K
authors.initials: EK
authors.lastname: Park
authors.forename: D Y
authors.initials: DY
authors.lastname: Zang
authors.forename: D Y
authors.initials: DY
authors.lastname: Jo
authors.forename: H W
authors.initials: HW
authors.lastname: Lee
authors.forename: Y-R
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001549:Benzamides / Q000493:pharmacokinetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D000075102:Organic Cation Transporter 2; D010879:Piperazines / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D010879:Piperazines; D011743:Pyrimidines; C491013:SLC22A2 protein, human; D000068877:Imatinib Mesylate; D001189:Aryl Hydrocarbon Hydroxylases