title: Mexican Childhood Acute Lymphoblastic Leukemia: A Pilot Study of the MDR1 and MTHFR Gene Polymorphisms and Their Associations with Clinical Outcomes.
abstract: BACKGROUND
  Genetic polymorphisms in patients with acute lymphoblastic leukemia (ALL) may influence the toxicity of chemotherapeutic agents. Due to the importance of the transport P-glycoprotein and methylenetetrahydrofolate reductase in the metabolism of chemotherapeutic agents, we analyzed the MDR1 rs1045642 and MTHFR rs1801133 polymorphisms and their associations with clinical outcomes in Mexican childhood ALL patients.
  
  
  METHODS
  A total of 109 patients participated in this study. The clinical evaluation consisted of a physical examination and a laboratory test. Genotyping of MDR1 rs1045642 (3435 C>T) and MTHFR rs1801133 (677 C>T) was performed by polymerase chain reaction/restriction fragment length polymorphism. Statistical analyses were performed using SPSS 14.0. The odds ratios and 95% confidence intervals (CI) were estimated by logistic regression.
  
  
  RESULTS
  Individuals who were CC homozygotes at MDR1 rs1045642 had lower risk of having methotrexate plasma concentrations >1 μM and leukopenia grade I (odds ratio [OR] = 0.30; 95% CI = 0.13-0.72 and OR = 0.32; 95% CI = 0.14-0.72, respectively). Patients who were CC homozygotes at MTHFR rs1801133 had a higher risk of developing mucositis (OR = 3.61; 95% CI = 1.42-9.14).
  
  
  CONCLUSIONS
  MDR1 rs1045642 and MTHFR rs1801133 should be considered as diagnostic candidates for the identification of pediatric patients with a high risk of suffering adverse events during ALL treatment.
authors.affiliation: 1 Departamento de Hemato-Oncologia, Hospital Infantil de Mexico , Federico Gomez, Mexico City, Mexico .
authors.forename: Arturo
authors.initials: A
authors.lastname: Ramírez-Pacheco
authors.affiliation: 1 Departamento de Hemato-Oncologia, Hospital Infantil de Mexico , Federico Gomez, Mexico City, Mexico .
authors.forename: Selene
authors.initials: S
authors.lastname: Moreno-Guerrero
authors.affiliation: 2 Escuela Nacional de Ciencias Biologicas , IPN, Mexico City, Mexico .
authors.forename: Ilse
authors.initials: I
authors.lastname: Alamillo
authors.affiliation: 1 Departamento de Hemato-Oncologia, Hospital Infantil de Mexico , Federico Gomez, Mexico City, Mexico .
authors.forename: Aurora
authors.initials: A
authors.lastname: Medina-Sanson
authors.affiliation: 3 Banco Central, Hospital Infantil de Mexico , Federico Gomez, Mexico City, Mexico .
authors.forename: Briseida
authors.initials: B
authors.lastname: Lopez
authors.affiliation: 1 Departamento de Hemato-Oncologia, Hospital Infantil de Mexico , Federico Gomez, Mexico City, Mexico .|4 Sociedad Mexicana de Salud Publica, CENAPRECE , SSA, Mexico City, Mexico .
authors.forename: Monica
authors.initials: M
authors.lastname: Moreno-Galván
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D006801:Humans; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008800:Mexico; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D010865:Pilot Projects; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D012307:Risk Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate
keywords: MDR1 polymorphisms; MTHFR polymorphisms; Mexican leukemia; childhood leukemia