Genetic polymorphisms and expression levels in miRNA and their contribution to pediatric acute myeloid leukemia: A focus on miR-146a and miR-499 variants

Abstract

Pediatric acute myeloid leukemia (AML) is a rare but curable hematologic malignancy. This study aims to investigate miR-146a rs2910164 G/C and miR-499 rs3746444 T/C in childhood AML.

Genotyping and expression analysis were performed in 214 AML pediatric patients in Iran.

The homozygous mutant genotypes of the miR-146a and miR-499 were related to approximately 2-fold increased risk of pediatric AML occurrence [(OR: 1.97, 95 %CI: 1.090–3.561; p = 0.024); (OR: 2.319; 95 % CI: 1.238–4.346; p = 0.008), respectively]. A significant difference in the frequency of the mutant allele C for miRNA-146a rs2910164 was observed in cases compared to the control group (OR: 1.64, 95 % CI: 1.221–2.207; p = 0.001). The combination of the miR-146a GG and miR-499 CC genotypes was over four times more frequent in AML patients (OR: 4.148; 95 % CI: 1.714–10.040; p = 0.001). MiR-146a and miR-499 expression levels are significantly upregulated in AML patients (2.1-fold and 1.4-fold, respectively); particularly, mutant genotypes of miR-146a and miR-499 showed 3.7-fold and 2.4-fold higher expression (p˂0.05). Based on our bioinformatics analysis data, the mutant allele C exhibited lower stability compared to the wild-type allele G, which may indicate a diminished binding affinity toward target mRNAs and consequently impairment of its regulatory function. Our results revealed that the presence of the mutant alleles is associated with an increased risk of pediatric AML and elevated miRNA expression levels.