title: A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report.
abstract: Growing evidence showed that microRNAs (miRs) are involved in normal hematopoiesis and the pathogenesis of several hematological malignancies. Genetic variations or mutations occurring in the miR gene region may affect the property of miRs through altering miR expression and/or maturation. The aim of the present study was to evaluate the possible relationship between two miRs polymorphisms, hsa-miR-146a (rs2910164 G>C) and hsa-miR-499 (rs3746444 T>C), and the susceptibility to childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. This case-control study was performed on 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group). Tetra-primer amplification refractory mutation system-polymerase chain reaction was applied for genotyping the variants. We found that the rs2910164 G>C variant of hsa-miR-146a significantly increased the risk of ALL (CC vs. GG, OR = 4.24, 95% CI = 1.52-11.87, P = 0.006; GC vs. GG, OR = 3.55, 95% CI = 1.41-8.93, P = 0.007; C vs. T, OR = 1.73, 95% CI = 1.13-2.67, P = 0.012). With respect to hsa-miR-499 rs3746444 T/C, no significant difference in allele and genotype frequencies of the rs3746444 variant between ALL patients and controls was observed. Our results for the first time demonstrated that the miR-146a rs2910164, but not miR-499 rs3746444 variant, was associated with increased risk for developing pediatrics ALL in an Iranian population.
authors.affiliation: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Seyed-Shahaboddin
authors.initials: SS
authors.lastname: Hasani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Omrani
authors.forename: Maryam
authors.initials: M
authors.lastname: Sheybani-Nasab
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012306:Risk
chemical_list: C542542:MIRN146 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs