title: Effect of folylpolyglutamate synthase A22G polymorphism on the risk and survival of patients with acute lymphoblastic leukemia.
abstract: Folylpolyglutamate synthase (FPGS) is the key enzyme that converts the chemotherapeutic agent, methotrexate (MTX), into MTX polyglutamate. An A22G polymorphism has been found in the FPGS gene. This study aimed to evaluated whether the A22G polymorphism in the FPGS gene is associated with an increased risk of acute lymphoblastic leukemia (ALL) and whether it plays a role in increasing the survival of patients with ALL. In this study, a total of 70 patients with ALL and 100 healthy individuals were genotyped by polymerase chain reaction and sequencing methods. The homozygous variant, 22G/G [odds ratio (OR)=3.88; 95% confidence interval (CI): 2.50-6.03] and the heterozygous variant, 22A/G (OR=1.37; 95% CI: 1.26-48.95) were risk factors for ALL. Patients with the 22A/G genotype had an OR of 1.81 (95% CI: 1.57-5.74; P=0.049) and carriers of the 22G/G genotype had an OR of 2.44 (95% CI: 2.40-11.82; P=0.017) for relapse. A significant association between the A22G polymorphism and survival of patients with ALL was found (P<0.05); whereas, individuals with A/G or G/G genotypes had a decreased overall survival (log-rank test, P=0.044). Although preliminary, these data suggest that the genotypes of the A22G polymorphism may be risk factors for ALL and may play a role in the survival of patients with ALL.
authors.affiliation: Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico.
authors.forename: Yazmín
authors.initials: Y
authors.lastname: Gómez-Gómez
authors.affiliation: Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Organista-Nava
authors.affiliation: Laboratory of Molecular Biomedicine, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Rangel-Rodriguez
authors.affiliation: Laboratory of Molecular Biomedicine, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
authors.forename: Berenice
authors.initials: B
authors.lastname: Illades-Aguiar
authors.affiliation: Laboratory of Toxicology and Environmental Health, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Moreno-Godínez
authors.affiliation: Laboratory of Cytopathology, School of Biological Sciences, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
authors.forename: Luz Del Carmen
authors.initials: LD
authors.lastname: Alarcón-Romero
authors.affiliation: Laboratory of Molecular Biomedicine, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Leyva-Vázquez
keywords: A22G polymorphism; acute lymphoblastic leukemia; folylpolyglutamate synthase; survival