Noncoding RNA-related polymorphisms in pediatric acute lymphoblastic leukemia susceptibility
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2014-03-11Autor
Martín Guerrero, Idoia
Piñán, María Ángeles
García Miguel, Purificación
Sánchez Toledo, José
Carbone Bañeres, Ana
Uriz, José Javier
Navajas Gutiérrez, Aurora
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Pediatric Research 75(6) : 767-773 (2014)
Resumen
Background: Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.5% of the entire genome. In acute lymphoblastic leukemia (ALL), it has been suggested that the expression of microRNAs (miRNAs) is dysregulated, which suggests that they may have a role in ALL risk. Changes in miRNA function may occur through single-nucleotide polymorphisms (SNPs). Therefore, the aim of this study was to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA-processing genes, contribute to a predisposition for childhood ALL.
Methods: In this study, we analyzed 118 SNPs in pre-miRNAs and miRNA-processing genes in 213 B-cell ALL patients and 387 controls.
Results: We found 11 SNPs significantly associated with ALL susceptibility. These included three SNPs present in miRNA genes (miR-612, miR-499, and miR-449b) and eight SNPs present in six miRNA biogenesis pathway genes (TNRC6B, DROSHA, DGCR8, EIF2C1, CNOT1, and CNOT6). Among the 118 SNPs analyzed, rs12803915 in mir-612 and rs3746444 in mir-499 exhibited a more significant association, with a P value <0.01.
Conclusion: The results of this study indicate that SNP rs12803915 located in pre-mir-612, and SNP rs3746444 located in pre-mir-499, may represent novel markers of B-cell ALL susceptibility.