Genetic Polymorphisms of MTRRA66G Genes and Susceptibility to Acute Lymphoblastic Leukemia in the Yemeni Population
Asian Hematology Research Journal,
Page 57-64
Abstract
Background: Folic acid metabolism has a major role in DNA methylation and synthesis. Genetic Polymorphisms in folate may disrupt enzyme activities and maybe affect the malignant risk.
Methionine synthase reductase <MTRR> are very important enzyme for the folate cycle.
Objectives: To study the possible relation between polymorphisms of MTRRA66G genes and susceptibility to acute lymphoblastic leukemia (ALL) in Yemeni patients.
Methods: A total of 115 patients with ALL attended oncology centers in Yemen and 140 unrelated healthy individuals as a control group was involved in a case-control study. DNA was extracted from collected EDTA venous blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP].
Results: The frequency of MTRR 66A-G heterozygous (AG), homozygous (GG) and wild type (AA) in cases was 52.2% (60), 22.6% (26), and 25.2% (29), respectively. Whereas, the frequency of MTRR 66A-G heterozygous (AG), homozygous (GG) and wild type (AA) in controls was 46.4% (65), 27.1% (38), and 26.4% (37), respectively. The difference in frequencies were statistically insignificant (P=0.471, OR = 1.065, 95% confidence interval (CI) 0.606–1.873).
Conclusion: Our finding for MTRR A66G polymorphism does not associate with the development of acute lymphoblastic leukemia in Yemeni patients.
Keywords:
- Acute lymphoblastic leukemia
- methionine synthase reductase
- polymorphism
- Yemen
How to Cite
Saleh, R., Musa, H. H., Hamid, G. A., & Hamid, M. M. A. (2022). Genetic Polymorphisms of MTRRA66G Genes and Susceptibility to Acute Lymphoblastic Leukemia in the Yemeni Population. Asian Hematology Research Journal, 6(4), 57-64. Retrieved from https://journalahrj.com/index.php/AHRJ/article/view/30211
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Brouns R, Ursem N, Lindemans J, Hop W, Pluijm S, Steegers‐Theunissen R. Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. Prenatal diagnosis. 2008;28:485-493.
Barbosa PR, Stabler SP, Machado AL, Braga RC, Hirata RD, Hirata MH, Sampaio-Neto LF, Allen RH, Guerra-Shinohara EM. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr. 2008;62(8):1010-21.
DOI: 10.1038/sj.ejcn.1602810 Epub 2007 May 23 PMID: 17522601
Brugada R, Marian AJ. A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. Atherosclerosis. 1997;128(1) :107-12.
DOI: 10.1016/s0021-9150(96)05977-1 PMID: 9051203
Gast A, Bermejo JL, Flohr T, Stanulla M, Burwinkel B, Schrappe M, Bartram CR, Hemminki K, Kumar R. Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: A case-control study. Leukemia. 2007;21(2):320-5.
DOI: 10.1038/sj.leu.2404474 Epub 2006 Nov 30 PMID: 17136115
Wang SS, Feng L, Qiao FY, Lv JJ. Functional variant in methionine synthase reductase decreases the risk of down syndrome in China. J Obstet Gynaecol Res. 2013;39(2):511-5.
DOI: 10.1111/j.1447-0756.2012.01978.x Epub 2012 Aug 26 PMID: 22925068
Grace DBA. Association of glutathione-S-transferase M1, P1, and T1 gene polymorphisms with treatment response in childhood acute lymphocytic leukemia. Acta Medica Philippina. 2016;50:75-80.
DOI: 10.1007/s10552-012-0004-0 Epub 2012 Jun 16. PMID: 22706675
Lautner-Csorba O, Gézsi A, Erdélyi DJ, Hullám G, Antal P, Semsei ÁF, Kutszegi N, Kovács G, Falus A, Szalai C. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis. PLoS One. 2013;8(8):e69843.
DOI: 10.1371/journal.pone.0069843
PMID: 23940529 PMCID: PMC3734218
Shah SJ, Taub JW, Witt TL, Pollock BH, Ding BC, Moore DS, Amylon M, Pullen J, Ravindranath Y, Matherly LH. Relationship of p15 and p16 gene alterations to elevated dihydrofolate reductase in childhood acute lymphoblastic leukaemia. Br J Haematol. 2001;113(3):746-56.
DOI: 10.1046/j.1365-2141.2001.02775.x PMID: 11380466
Robien K, Ulrich CM. 5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol. 2003;157(7):571-82
DOI: 10.1093/aje/kwg024 PMID: 12672676
Kim HN, Kim YK, Lee IK, Yang DH, Lee JJ, Shin MH, Park KS, Chol JS, Park MR, Jo DY. Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies. Leukemia Research. 2009;33:82-87.
Gemmati D, Ongaro A, Scapoli GL, Della Porta M, Tognazzo S, Serino ML, Di Bona E, Rodeghiero F, Gilli G, Reverberi R, Caruso A, Pasello M, Pellati A, De Mattei M. Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults. Cancer Epidemiol Biomarkers Prev. 2004;13(5):787-94. PMID: 15159311
Petra BG, Janez J, Vita D. Gene-gene interactions in the folate metabolic pathway influence the risk for acute lymphoblastic leukemia in children. Leuk Lymphoma. 2007;48(4):786-92.
DOI: 10.1080/10428190601187711 PMID: 17454638
Gra O, Glotov A, Kozhekbayeva ZM, Makarova O, Nasedkina T. Genetic polymorphism of GST, NAT2, and MTRR and susceptibility to childhood acute leukemia. Molecular Biology. 2008a;42:187.
Koppen IJ, Hermans FJ, Kaspers GJ. Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol. 2010;148(1):3-14.
DOI: 10.1111/j.1365-2141.2009.07898.x Epub 2009 Sep 22 PMID: 19775302
Wagiman SN, Husin NH, Abd Latiff Z, Alias H, Jamal R and Zakaria SZS. Folate-related genes polymorphisms associated with the risk of childhood leukaemia in the Malaysian population. Asia-Pacific Journal of Molecular Medicine. 2011;1:1-10. ISSN 2232-0326
Fang DH, Ji Q, Fan CH, An Q, Li J. Methionine synthase reductase A66G polymorphism and leukemia risk: Evidence from published studies. Leuk Lymphoma. 2014;55(8):1910-4.
DOI: 10.3109/10428194.2013.867492 Epub 2014 Jan 24 PMID: 24261678
Wang P, Li S, Wang M, He J, Xi S. Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies. Journal of Cancer. 2017;8(2):266-277. Available:https://doi.org/10.7150/jca.17379
Saleh R, Musa HH, Hamid GA, Hamid MM. Frequencies of GSTP1 (Ile105val) polymorphism and its association with acute lymphoblastic leukemia in Yemeni patients.
Hanson MR, Mulvihill JJ Epidemiology of child-blood cancer in Levine AS, cancer in the young. NewYork: Masson. 1980:3-12.
Gurney JG, Davis S, Severson RK, Fang JY, Ross JA, Robison LL. Trends in cancer incidence among children in the US. Cancer. 1996;78:532–541.
Radfan Hassan, Hussein Musa, Gamal Abdul Hamid et al. Epidemiological study in acute lymphoblastic leukemia in Yemen. European Journal of Pharmaceutical Sciences; 2017.
Abdul Hamid G. clinicoepidemiological features of adult leukemias in Aden, Yemen. Indian journal of applied research. 2015;5(7):334.
Abdul Hamid G. The pattern of hematological malignancies at Al-Gamhouria Teaching Hospital, Aden, Yemen, from 2008 to 2010. Turk J Hematol. 2012;29(4):342-347.
Abdul Hamid G, Akrabi MA. “Aberrant antigen expression in patients with acute leukemia”. EC Clinical and Medical Case Reports. 2019;2(3):53-60.
Abdul Hamid G, Ben Harize I. Bone marrow morphology and cytochemical staining in diagnosis and classification of acute leukemia. European Journal of Biomedical. 2018;5(8):574-583.
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. Environmental and chemical carcinogenesis. Semin Cancer Biol. 2004;14(6):473-86.
DOI: 10.1016/j.semcancer.2004.06.010
PMID: 15489140
Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, Gravel RA, Rozen R. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab. 1999;67(4):317-23.
DOI: 10.1006/mgme.1999.2879 PMID: 10444342
Brouns R, Ursem N, Lindemans J, Hop W, Pluijm S, Steegers‐Theunissen R. Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. Prenatal diagnosis. 2008;28:485-493.
Barbosa PR, Stabler SP, Machado AL, Braga RC, Hirata RD, Hirata MH, Sampaio-Neto LF, Allen RH, Guerra-Shinohara EM. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr. 2008;62(8):1010-21.
DOI: 10.1038/sj.ejcn.1602810 Epub 2007 May 23 PMID: 17522601
Brugada R, Marian AJ. A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. Atherosclerosis. 1997;128(1) :107-12.
DOI: 10.1016/s0021-9150(96)05977-1 PMID: 9051203
Gast A, Bermejo JL, Flohr T, Stanulla M, Burwinkel B, Schrappe M, Bartram CR, Hemminki K, Kumar R. Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: A case-control study. Leukemia. 2007;21(2):320-5.
DOI: 10.1038/sj.leu.2404474 Epub 2006 Nov 30 PMID: 17136115
Wang SS, Feng L, Qiao FY, Lv JJ. Functional variant in methionine synthase reductase decreases the risk of down syndrome in China. J Obstet Gynaecol Res. 2013;39(2):511-5.
DOI: 10.1111/j.1447-0756.2012.01978.x Epub 2012 Aug 26 PMID: 22925068
Grace DBA. Association of glutathione-S-transferase M1, P1, and T1 gene polymorphisms with treatment response in childhood acute lymphocytic leukemia. Acta Medica Philippina. 2016;50:75-80.
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