Research Article

The Association of rs2114358 in the miR-1206 Polymorphism to Chronic Myeloid Leukemia

Author(s): Fathelrahman Mahdi Hassan*

Volume 8, Issue 3, 2019

Page: [248 - 252] Pages: 5

DOI: 10.2174/2211536608666190102143439

Price: $65

Abstract

Introduction: Association studies with factor candidates have advised that single nucleotide polymorphisms (SNPs) could also be related to CML progression and to the response to medical care. Genetic variation in miR-1206 of both derived and neighborhood SNPs process genes will contribute to the predisposition to cancer. The role of those with the risk of CML has not been extensively studied. Therefore, the aim of this study was to evaluate whether polymorphisms in rs2114358 in pre-miRNAs process genes contribute to the risk of CML.

Methods: A cross-sectional study was conducted during the period of March 2016 to October 2017 in Khartoum state teaching hospitals. The study population included a total of 420 patients who were previously diagnosed of having CML and 220 cancer-free controls of both gender and were of the same age range. Peripheral blood and bone marrow aspiration samples were collected from patients (254 males, 166 females; median age 58.5 years, range from less than 50 and above 50 years old) and investigated after written informed consent was obtained. Patients were in chronic phase (n=212), accelerated phase (n=125), and blast (n=83). All the patients were under treatment using chemotherapy regiments. The rs2114358 SNP in pre-miRNA was selected for genotyping.

Results: The genotyping success rate was 98.3%. Genotype frequencies of the derived SNP and the neighborhood rs2114358 of miR-1206 compared to the controls were significantly different under Hardy-Weinberg Equilibrium (P=0.0001 and 0.0001 respectively). Significant differences were found in allele distributions of this SNP (P<0.01 and P<0.01). In total, the derived variant C allele of rs2114358 (OR=0.168, 95% CI=0.13-0.22) and G allele of neighborhood rs2114358 (OR=0.561, 95% CI=0.44-0.72) in patients' group were associated with an increased risk of CML compared to a control group. Patients with rs2114358 CC genotype (P = 0.0001) or TC (P = 0.0001) and the neighborhood rs2114358 GA genotype (P = 0.0460) or GG (P = 0.0093) were obviously much higher than that of the TT and AA genotype's patients.

Conclusion: In conclusion, we discovered the association of SNP rs2114358 in miR-1206 with the risk of CML patients, though more investigations are still required to understand the regulative mechanisms of this miR SNP with the target genes resulting in its dysregulation.

Keywords: Allele, CML risk, genotypes, leukemia, polymorphism, SNP rs2114358.

Graphical Abstract

[1]
Walid A, Abdulsamad W, Faten M, Thomas L. A chronic myeloid leukemia case with a unique variant Philadelphia translocation: t(9; 22; 21) (q34; q11; p12). Oncol Lett 2012; 3(5): 1027-9.
[2]
Boultwood J, Perry J, Zaman R, et al. High-density single nucleotide polymorphism arrayanalysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010; 24: 1139-45.
[3]
Zhang SJ, Shi JY, Li JY. GATA-2L359 V mutation is exclusively associated with CML progression but no other hematological malignancies and GATA-2 P250A is a novel single nucleotide polymorphism. Leuk Res 2009; 33: 1141-3.
[4]
Angelini S, Soverini S, Ravegnini G, et al. Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy. Haematologica 2013; 98: 193-200.
[5]
Crossman LC, O’Hare T, Lange T, et al. A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib. Leukemia 2005; 19: 1859-62.
[6]
Kim DH, Xu W, Ma C, et al. Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia. Blood 2009; 113: 2517-25.
[7]
Liu YC, Hsiao HH, Yang WC, et al. MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: the association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib. Mol Carcinog 2014; 53: 951-9.
[8]
Ma X, Ruan G, Wang Y, et al. Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5′ regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population. Clin Cancer Res 2005; 11: 8592-9.
[9]
Heriberto B, Juan RG, François S, et al. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget 2015; 6(34): 36269-77.
[10]
Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell 2012; 149: 515-24.
[11]
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136: 215-33.
[12]
Rukov JL, Shomron N. MicroRNA pharmacogenomics: post-transcriptional regulation of drug response. Trends Mol Med 2011; 17: 412-23.
[13]
Sclafani F, Chau I, Cunningham D, et al. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients. Carcinogenesis 2016; 37: 852-7.
[14]
Yong M, Chengda Z, Fanyi M, Jiehong K, Weipeng W, Dong H. The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients. Oncotarget 2018; 9(6): 6793-9.
[15]
Sand M, Skrygan M, Sand D, et al. Expression of microRNAs in basal cell carcinoma. Br J Dermatol 2012; 167: 847-55.
[16]
Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001; 291(5507): 1304-51.
[17]
Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 2010; 10: 389-402.
[18]
Qiaoli Z, Jiang C, Nada H, et al. Single nucleotide polymorphisms in apoptosis pathway are associated with response to imatinib therapy in chronic myeloid leukemia. J Transl Med 2016; 14: 82.
[19]
Kim HK, Prokunina-Olsson L, Chanock SJ. Common genetic variants in miR-1206 (8q24.2) and miR-612 (11q13.3) affect biogenesis of mature miRNA forms. PLoS One 2012; 7: e47454.
[20]
Martin-Guerrero I, Gutierrez-Camino A, Lopez-Lopez E, et al. Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia. PLoS One 2015; 10: e0118905.
[21]
Huppi K, Volfovsky N, Runfola T, et al. The identification of microRNAs in a genomically unstable region of human chromosome 8q24. Mol Cancer Res 2008; 6: 212-21.
[22]
López-López E, Gutiérrez-Camino Á, Piñán MA, et al. Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia. PLoS One 2014; 9: e91261.
[23]
Gutierrez-Camino A, Oosterom N, den Hoed MA, et al. The miR-1206 microRNA variant is associated with methotrexate-induced oral mucositis in pediatric acute lymphoblastic leukemia. Pharmacogenet Genomics 2017; 27: 303-6.
[24]
Idoia MG, Angela GC, Elixabet LL, et al. Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia. PLoS One 2015; 10(3): e0118905.

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