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


ABSTRACT:

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.

SUBMITTER: Jimenez-Morales S 

PROVIDER: S-EPMC8602911 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Jiménez-Morales Silvia S   Núñez-Enríquez Juan Carlos JC   Cruz-Islas Jazmín J   Bekker-Méndez Vilma Carolina VC   Jiménez-Hernández Elva E   Medina-Sanson Aurora A   Olarte-Carrillo Irma I   Martínez-Tovar Adolfo A   Flores-Lujano Janet J   Ramírez-Bello Julian J   Pérez-Saldívar María Luisa ML   Martín-Trejo Jorge Alfonso JA   Pérez-Lorenzana Héctor H   Amador-Sánchez Raquel R   Mora-Ríos Felix Gustavo FG   Peñaloza-González José Gabriel JG   Duarte-Rodríguez David Aldebarán DA   Torres-Nava José Refugio JR   Flores-Bautista Juan Eduardo JE   Espinosa-Elizondo Rosa Martha RM   Román-Zepeda Pedro Francisco PF   Flores-Villegas Luz Victoria LV   Tamez-Gómez Edna Liliana EL   López-García Víctor Hugo VH   Lara-Ramos José Ramón JR   González-Ulivarri Juana Esther JE   Martínez-Silva Sofía Irene SI   Espinoza-Anrubio Gilberto G   Almeida-Hernández Carolina C   Ramírez-Colorado Rosario R   Hernández-Mora Luis L   García-López Luis Ramiro LR   Cruz-Ojeda Gabriela Adriana GA   Godoy-Esquivel Arturo Emilio AE   Contreras-Hernández Iris I   Medina-Hernández Abraham A   López-Caballero María Guadalupe MG   Hernández-Pineda Norma Angélica NA   Granados-Kraulles Jorge J   Rodríguez-Vázquez María Adriana MA   Torres-Valle Delfino D   Cortés-Reyes Carlos C   Medrano-López Francisco F   Pérez-Gómez Jessica Arleet JA   Martínez-Ríos Annel A   Aguilar-De-Los-Santos Antonio A   Serafin-Díaz Berenice B   Gutiérrez-Rivera María de Lourdes ML   Merino-Pasaye Laura Elizabeth LE   Vargas-Alarcón Gilberto G   Mata-Rocha Minerva M   Sepúlveda-Robles Omar Alejandro OA   Rosas-Vargas Haydeé H   Hidalgo-Miranda Alfredo A   Mejía-Aranguré Juan Manuel JM  

Frontiers in oncology 20211105


<h4>Background</h4>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 <i>miR-146a</i>, <i>miR-196a-2</i>, <i>miR-499a</i>, and <i>miR-612</i> genes are associated with the risk to ALL in pediatric M  ...[more]

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