title: Arginine homozygosity in codon 72 of p53 correlates with failure to imatinib response in chronic myeloid leukemia.
abstract: OBJECTIVE
  In this study, the role of the polymorphism at codon 72 of tumor protein p53 gene (TP53) was investigated regarding the response to treatment with imatinib in chronic myeloid leukemia (CML).
  
  
  METHODS
  A total of 85 patients with CML were treated according to the Brazilian National Cancer Institute (INCA) guidelines and at the end of the 18th month a blood sample were collected for genotyping. Genomic DNA was extracted and TP53 codon 72 genotyping was performed by allele-specific polymerase chain reaction (AS-PCR), which detects argine or proline alleles.
  
  
  RESULTS
  Of the 85 CML samples, 27 samples were homozygous for arginine (Arg/Arg), 12 homozygous for proline (Pro/Pro) and 46 samples heterozygous (Arg/Pro). TP53 codon 72 polymorphism was in Hardy-Weinberg equilibrium (χ(2)=1.17, P=0.37). We did not find significant association between codon 72 polymorphism and age at diagnosis and sex (P=0.76 and P=0.33, respectively). High Sokal score are significantly associated with Arg/Arg genotype carriers (Odds ratio, OR=4.09; 95% confidence interval, CI 1.01=15.89; P=0.036). The arginine allele in homozygosis also have an increased risk of failure response to imatinib when compared with both, the heterozygous (Arg/Pro) and proline homozygous patients (P=0.021; OR=2.99, 95% CI=1.16-7.67). Additionally, interaction analysis with age at diagnosis revealed that among patients over 40-yr old, Arg/Arg genotype was significantly associated with non-responder patients (P=0.007; OR=5.13, 95% CI=1.5-17.55).
  
  
  CONCLUSIONS
  The findings suggest that in CML patients, TP53 codon 72 polymorphism may contribute to a high Sokal score and failure to imatinib treatment.
authors: Department of Biochemistry and Molecular Biology, Biological Sciences Institute, Universidade Federal de Goiás, Campus II, Jardim Samambaia, CP 131, 74001-970, Goiânia GO, Brazil.
authors: Jeany
authors: J
authors: Camelo-Santos
authors: Adriana
authors: A
authors: do Prado Barbosa
authors: Elisangela
authors: E
authors: de Paula Silveira-Lacerda
authors: Lidia Andreu
authors: LA
authors: Guillo
mesh_terms: D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001120:Arginine / Q000235:genetics*; D001549:Benzamides / Q000627:therapeutic use*; D003062:Codon; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D003062:Codon; D010879:Piperazines; D011743:Pyrimidines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000068877:Imatinib Mesylate; D001120:Arginine; D011392:Proline