miR-146a, miR-196a2, miR-499, and miR-149 linked with susceptibility to acute lymphoblastic leukemia: A case-control study in Tunisia
Dhiflaoui A. Mahjoub S. Chayeb V. Achour B. Chouchen S. Abdennebi H.B. Mahjoub T. Almawi W.Y.
5 August 2022Elsevier B.V.
Gene
2022#834
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.
Acute lymphoblastic leukemia , Biomarkers , Case‑control study , microRNA , Single nucleotide polymorphisms
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Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, Tunisia
Department of Clinical Hematology, CHU Farhat Hached, Sousse, Tunisia
Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
Nazarbayev University School of Medicine, Nur-Sultan (Astana), Kazakhstan
Laboratory of Human Genome and Multifactorial Diseases (LR12ES07)
Department of Clinical Hematology
Faculty of Pharmacy of Monastir
Nazarbayev University School of Medicine
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