Frontiers in Oncology (Nov 2021)

Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia

  • Silvia Jiménez-Morales,
  • Juan Carlos Núñez-Enríquez,
  • Jazmín Cruz-Islas,
  • Vilma Carolina Bekker-Méndez,
  • Elva Jiménez-Hernández,
  • Aurora Medina-Sanson,
  • Irma Olarte-Carrillo,
  • Adolfo Martínez-Tovar,
  • Janet Flores-Lujano,
  • Julian Ramírez-Bello,
  • María Luisa Pérez-Saldívar,
  • Jorge Alfonso Martín-Trejo,
  • Héctor Pérez-Lorenzana,
  • Raquel Amador-Sánchez,
  • Felix Gustavo Mora-Ríos,
  • José Gabriel Peñaloza-González,
  • David Aldebarán Duarte-Rodríguez,
  • José Refugio Torres-Nava,
  • Juan Eduardo Flores-Bautista,
  • Rosa Martha Espinosa-Elizondo,
  • Pedro Francisco Román-Zepeda,
  • Luz Victoria Flores-Villegas,
  • Edna Liliana Tamez-Gómez,
  • Víctor Hugo López-García,
  • José Ramón Lara-Ramos,
  • Juana Esther González-Ulivarri,
  • Sofía Irene Martínez-Silva,
  • Gilberto Espinoza-Anrubio,
  • Carolina Almeida-Hernández,
  • Rosario Ramírez-Colorado,
  • Luis Hernández-Mora,
  • Luis Ramiro García-López,
  • Gabriela Adriana Cruz-Ojeda,
  • Arturo Emilio Godoy-Esquivel,
  • Iris Contreras-Hernández,
  • Abraham Medina-Hernández,
  • María Guadalupe López-Caballero,
  • Norma Angélica Hernández-Pineda,
  • Jorge Granados-Kraulles,
  • María Adriana Rodríguez-Vázquez,
  • Delfino Torres-Valle,
  • Carlos Cortés-Reyes,
  • Francisco Medrano-López,
  • Jessica Arleet Pérez-Gómez,
  • Annel Martínez-Ríos,
  • Antonio Aguilar-De-los-Santos,
  • Berenice Serafin-Díaz,
  • María de Lourdes Gutiérrez-Rivera,
  • Laura Elizabeth Merino-Pasaye,
  • Gilberto Vargas-Alarcón,
  • Minerva Mata-Rocha,
  • Omar Alejandro Sepúlveda-Robles,
  • Haydeé Rosas-Vargas,
  • Alfredo Hidalgo-Miranda,
  • Juan Manuel Mejía-Aranguré,
  • Juan Manuel Mejía-Aranguré,
  • Juan Manuel Mejía-Aranguré

DOI
https://doi.org/10.3389/fonc.2021.762063
Journal volume & issue
Vol. 11

Abstract

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BackgroundAcute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population.MethodsA multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5′exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software.ResultsmiR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05–2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23–23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04–298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found.ConclusionOur findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.

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