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Polymorphism G80A in the Reduced Folate Carrier Gene and its Relationship to Survival and Risk of Relapse in Acute Lymphoblastic Leukemia
  1. Marco Antonio Leyva-Vázquez, PhD*,
  2. Jorge Organista-Nava, MSc,
  3. Yazmín Gómez-Gómez, MSc,
  4. Adriana Contreras-Quiroz, MSc*,
  5. Eugenia Flores-Alfaro, PhD,
  6. Berenice Illades-Aguiar, PhD*
  1. From the *Laboratory of Molecular Biomedicine, School of Biological Sciences, Guerrero State University, Chilpancingo, Guerrero; †Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), University City, DF; and ‡Laboratory of Chronic Degenerative Diseases and Infections, School of Biological Sciences, Guerrero State University, Chilpancingo, Guerrero, Mexico.
  1. Received February 7, 2012, and in revised form June 20, 2012.
  2. Accepted for publication June 23, 2012.
  3. Reprints: Marco Antonio Leyva-Vázquez, PhD, Laboratory of Molecular Biomedicine, School of Biological Sciences, Guerrero State University, Av Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, México 39090. E-mail: leyvamarco13{at}gmail.com.
  4. MALV, JON, and YGG contributed equally to this study; MALV, JON, YGG, and BIA designed the study, analyzed and interpreted data, and drafted the manuscript; JON, YGG, EFA, and ACQ contributed to data collection; MALV and BIA revised and approved the final version of the paper.
  5. All authors have no conflicts of interest to declare.

Abstract

Background The reduced folate carrier (RFC1) is a major methotrexate transporter whose impaired function was recognized as a frequent mechanism of antifolate resistance. Recently, a G80A polymorphism has been described in the RFC1. This study evaluated the effect of the G80A polymorphism in the RFC1 gene on survival and risk of relapse of acute lymphoblastic leukemia.

Methods and Results Seventy patients with acute lymphoblastic leukemia were genotyped by polymerase chain reaction restriction fragment length polymorphism method. An association between the polymorphism and risk of relapse was found (P < 0.05). Patients with the G/A genotype have 3.97 (95% confidence interval, 1.12–14.06) and carriers of the A/A genotype have 7.84 (95% confidence interval, 1.66–37.10) higher chance of a relapse. Other variables such as age and leukocyte count were associated (P < 0.05) with the risk of relapse of disease. Individuals with G/A or A/A genotypes had poorer survival (log-rank test, P = < 0.05).

Conclusions These data suggest a role of the polymorphism G80A in the risk of relapse and the mortality risk in patients with acute lymphoblastic leukemia from the State of Guerrero, Mexico.

Key Words
  • acute lymphoblastic leukemia
  • reduced folate carrier
  • risk of relapse
  • G80A polymorphism

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