Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia
Authors: Jiménez-Morales Silvia , Núñez-Enríquez Juan Carlos , Cruz-Islas Jazmín , Bekker-Méndez Vilma Carolina , Jiménez-Hernández Elva , Medina-Sanson Aurora , Olarte-Carrillo Irma , Martínez-Tovar Adolfo , Flores-Lujano Janet , Ramírez-Bello Julian , Pérez-Saldívar María Luisa , Martín-Trejo Jorge Alfonso , Pérez-Lorenzana Héctor , Amador-Sánchez Raquel , Mora-Ríos Felix Gustavo , Peñaloza-González José Gabriel , Duarte-Rodríguez David Aldebarán , Torres-Nava José Refugio , Flores-Bautista Juan Eduardo , Espinosa-Elizondo Rosa Martha , Román-Zepeda Pedro Francisco , Flores-Villegas Luz Victoria , Tamez-Gómez Edna Liliana , López-García Víctor Hugo , Lara-Ramos José Ramón , González-Ulivarri Juana Esther , Martínez-Silva Sofía Irene , Espinoza-Anrubio Gilberto , Almeida-Hernández Carolina , Ramírez-Colorado Rosario , Hernández-Mora Luis , García-López Luis Ramiro , Cruz-Ojeda Gabriela Adriana , Godoy-Esquivel Arturo Emilio , Contreras-Hernández Iris , Medina-Hernández Abraham , López-Caballero María Guadalupe , Hernández-Pineda Norma Angélica , Granados-Kraulles Jorge , Rodríguez-Vázquez María Adriana , Torres-Valle Delfino , Cortés-Reyes Carlos , Medrano-López Francisco , Pérez-Gómez Jessica Arleet , Martínez-Ríos Annel , Aguilar-De-los-Santos Antonio , Serafin-Díaz Berenice , Gutiérrez-Rivera María de Lourdes , Merino-Pasaye Laura Elizabeth , Vargas-Alarcón Gilberto , Mata-Rocha Minerva , Sepúlveda-Robles Omar Alejandro , Rosas-Vargas Haydeé , Hidalgo-Miranda Alfredo , Mejía-Aranguré Juan Manuel 
Published: November 2021

Background

Acute 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.

Methods

A 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.

Results

miR-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.

Conclusion

Our 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.