miR-146a, miR-196a2, miR-499, and miR-149 linked with susceptibility to acute lymphoblastic leukemia: A case-control study in Tunisia.

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are promising biomarkers of hematological malignancies, including acute lymphoblastic leukaemia (ALL). Recent studies revealed that miRNA single nucleotide polymorphisms (miR-SNP) modulate cancer risk by regulating various signaling pathways. However, their association with altered risk of ALL yielded inconsistent results. OBJECTIVE: This study aims to investigate the association of four miR-SNPs with altered risk of ALL risk in Tunisian, the first on North African population. METHODS: A retrospective case-control study exploring the association of miR-146a, miR-196a2, miR-499, and miR-149 SNPs in 126 ALL patients and 126 healthy controls. RESULTS: Of the tested variants, significantly lower minor allele frequencies (MAF) of miR-146a C-allele and higher MAF frequency of miR-149 T-allele (P = 0.006) were seen in ALL cases. The association of miR-149 rs2292832 (Pc = 0.02), but not miR-146a rs2910164 (Pc = 0.11) persisted after correcting for multiple comparisons. Significantly reduced prevalence of miR-146a G/C genotype and higher frequency of miR-149 C/T genotype were seen in ALL cases vs. control subjects, which translated into negative association of miR-146a (rs2910164) with ALL according to the codominant and dominant models. Similarly, miR-149 (rs2292832) was positively associated with ALL according to the codominant and dominant genetic models. Three combinations comprising miR-146a/miR-196a2 GG vs CT + TT genotype combination, miR-146a/miR-499 GG vs TC + CC genotype combination, and miR-146a/miR-149 GG vs CT + TT genotype combination, were less frequent in ALL patients than in controls, and were negatively associated with the presence of ALL. CONCLUSION: Our study suggests that miR-146a and miR-149 polymorphisms constitute biomarkers for personalized diagnosis of ALL.