title: Functional polymorphism of CYP2B6 G15631T is associated with hematologic and cytogenetic response in chronic myeloid leukemia patients treated with imatinib.
abstract: In the spite of the impressive results achieved with imatinib in chronic myeloid leukemia (CML) patients, differences in patient's response are observed, which may be explained by interindividual genetic variability. It is known that cytochrome P450 enzymes play a major role in the metabolism of imatinib. The present study aimed to understand the functional impact of CYP2B6 15631G>T polymorphism on the response of imatinib in CML patients and its relation to CML susceptibility. We have genotyped CYP2B6 G15631T in 48 CML patients and 64 controls by PCR-RFLP. CYP2B6 15631G>T was not found to be a risk factor for CML (OR 95 % CI, 1.12, 0.6-2, p > 0.05). Hematologic response loss was higher in patients with 15631GG/TT genotype when compared with 15631GT (36.8 vs. 13.8 %; X (2) = 3.542, p = 0.063). Complete cytogenetic response was higher in 15631GG/GT genotype groups when compared with 15631TT (X (2) = 3.298, p = 0.024). Primary cytogenetic resistance was higher in patients carrying 15631GG/TT genotype when compared with 15631GT carriers (52.6 vs. 17.2 %; X (2) = 6.692, p = 0.010). Furthermore, side effects were more common for patients carrying 15631GG genotypes when compared with GT/TT carriers (36 vs. 13.8 %; X (2) = 8.3, p = 0.004). In light of our results, identification of 15631G>T polymorphism in CML patients might be helpful to predict therapeutic response to imatinib.
authors.affiliation: Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, University Hassan II, 19 Rue Tarik Ibnou Ziad, BP 9154, Casablanca, Morocco, kassoy2@yahoo.fr.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Kassogue
authors.forename: Meryem
authors.initials: M
authors.lastname: Quachouh
authors.forename: Hind
authors.initials: H
authors.lastname: Dehbi
authors.forename: Asma
authors.initials: A
authors.lastname: Quessar
authors.forename: Said
authors.initials: S
authors.lastname: Benchekroun
authors.forename: Sellama
authors.initials: S
authors.lastname: Nadifi
mesh_terms: D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001549:Benzamides / Q000627:therapeutic use*; D016022:Case-Control Studies; D065702:Cytochrome P-450 CYP2B6; D020732:Cytogenetic Analysis; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009018:Morocco; D010597:Pharmacogenetics; D010879:Piperazines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6