Angiotensin-converting Enzyme Insertion/Deletion Polymorphism (rs4646994) and Susceptibility to Acute Lymphoblastic Leukemia: A Case–control Study

Al Romisa Ahmed Abdulaziz; Elshazali Widaa Ali

doi:10.3889/oamjms.2022.9341

Authors

Al Romisa Ahmed Abdulaziz Department of Haematology, Faculty of Medical Laboratory Science, Sudan University for Science and Technology, Khartoum, Sudan
Elshazali Widaa Ali Department of Medical Laboratory Science, College of Applied Medical Science, University of Bisha, Bisha, Saudi Arabia; Department of Haematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan https://orcid.org/0000-0003-2787-2055

DOI:

https://doi.org/10.3889/oamjms.2022.9341

Keywords:

Angiotensin-converting enzyme, Insertion/deletion polymorphism, Acute lymphoblastic leukemia

Abstract

BACKGROUND: Angiotensin-converting enzyme (ACE) stimulates the proliferation of bone marrow hematopoietic progenitors and thought to be involved in pathological neoplastic hematopoiesis and leukemogenesis.

AIM: This study aimed to investigate the association between ACE gene I/D polymorphism and the risk of acute lymphoblastic leukemia (ALL).

MATERIALS AND METHODS: A total of 96 subjects were recruited for the study, 48 patients with ALL, and 48 apparently healthy volunteers as a control group. Genomic DNA was extracted from peripheral leukocytes and ACE I/D polymorphism was analysed using allele-specific polymerase chain reaction.

RESULTS: In both study groups, the ACE D/D polymorphic genotype was the most frequent (52.1% and 54.2%, respectively), followed by the ID genotype (47.9% and 45.8% respectively), while the II genotype was completely absent in both study groups. The distribution of the polymorphic genotypes among the study groups was not significantly different (p = 0. 0.398). The frequency of the D allele was 0.76 in the patients and 0.77 in the control group, while the frequency of I allele was 0.24 in the patients and 0.23 in the control group. No deviation from Hardy–Weinberg equilibrium was observed (χ²= 4.24, df = 1, p = 0.12).

CONCLUSION: ACE I/D polymorphism is not associated with susceptibility to ALL among the Sudanese population.

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References

Onciu M. Acute lymphoblastic leukaemia. Hematol Oncol Clin North Am. 2009;23(4):655-74. https://doi.org/10.1016/j.hoc.2009.04.009 PMid:19577163

Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet. 2020;395(10230):1146-62. https://doi.org/10.1016/S0140-6736(19)33018-1 PMid:32247396

Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013;381(9881):1943-55. https://doi.org/10.1016/S0140-6736(12)62187-4 PMid:23523389

Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2005;80(11):1517-27. https://doi.org/10.4065/80.11.1517 PMid:16295033

Bungaro S, Dell’Orto MC, Zangrando A, Basso D, Gorletta T, Nigro LL, et al. Integration of genomic and gene expression data of childhood ALL without known aberrations identifies subgroups with specific genetic hallmarks. Genes Chromosomes Cancer. 2009;48(1):22-38. https://doi.org/10.1002/gcc.20616 PMid:18803328

Usvasalo A, Räty R, Harila-Saari A, Koistinen P, Savolainen ER, Vettenranta K, et al. Acute lymphoblastic leukaemias with normal karyotypes are not without genomic aberrations. Cancer Genet Cytogenet. 2009;192(1):10-7. https://doi.org/10.1016/j.cancergencyto.2009.02.015 PMid:19480931

Teitell MA, Pandolfi PP. Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol. 2009;4:175-98. https://doi.org/10.1146/annurev.pathol.4.110807.092227 PMid:18783329

Wulf GG, Jahns-Streubel G, Nobiling R, Strutz F, Hemmerlein B, Hiddemann W, et al. Renin in acute myeloid leukaemia blasts. Br J Haematol. 1998;100(2):335-7. https://doi.org/10.1046/j.1365-2141.1998.00565.x PMid:9488623

Abali H, Haznedaroglu IC, Goker H, Celik I, Ozatli D, Koray Z, et al. Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: Preliminary evidences. Hematology. 2002;7(2):75-82. https://doi.org/10.1080/10245330290022160 PMid:12186695

Rodgers KE, Dizerega GS. Contribution of the local RAS to hematopoietic function: A novel therapeutic target. Front Endocrinol (Lausanne). 2013;4:157. https://doi.org/10.3389/fendo.2013.00157 PMid:24167502

Vairaktaris E, Yapijakis C, Tsigris C, Vassiliou S, Derka S, Nkenke E, et al. Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with increased risk for oral cancer. Acta Oncol. 2007;46:1097-102. https://doi.org/10.1080/02841860701373579 PMid:17851834

Nacak M, Nacak I, Sanli M, Ozkur M, Pektas M, Aynacioglu AS. Association of angiotensin converting enzyme gene insertion/ deletion polymorphism with lung cancer in Turkey. Cancer Genet Cytogenet. 2010;198:22-26. https://doi.org/10.1016/j.cancergencyto.2009.11.019 PMid:20303010

Sugimoto M, Furuta T, Shirai N, Ikuma M, Sugimura H, Hishida A. Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on gastric cancer risks in Japan. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1929-34. https://doi.org/10.1158/1055-9965.EPI-06-0339 PMid:17035401

Yigit B, Bozkurt N, Narter F, Yilmaz H, Yucebas E, Isbir T. Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis. Anticancer Res. 2007;27(2):933-6. PMid:17465223

Haiman CA, Henderson SO, Bretsky P, Kolonel LN, Henderson BE. Genetic variation in angiotensin I-converting enzyme (ACE) and breast cancer risk: The multiethnic cohort. Cancer Res. 2003;63(20):6984-7. PMid:14583500

Rocken C, Lendeckel U, Dierkes J, Westphal S, Carl-McGrath S, Peters B, et al. The number of lymph node metastases in gastric cancer correlates with the angiotensin I-converting enzyme gene insertion/deletion polymorphism. Clin Cancer Res. 2005;11(7):2526-30. https://doi.org/10.1158/1078-0432.CCR-04-1922 PMid:15814629

Mattei MG, Hubert C, Alhenc-Gelas F, Roeckel N, Corvol P, Soubrier F. Angiotensin I converting enzyme gene is on chromosome 17. Cytogenet Cell Genet. 1989;51:1041-45.

Hubert C, Houot AM, Corvol P, Soubrier F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem. 1991;266(23):15377-83. PMid:1651327

Crisan D, Carr J. Angiotensin I-converting enzyme: Genotype and disease associations. J Mol Diagn. 2000;2(3):105-15. https://doi.org/10.1016/S1525-1578(10)60624-1 PMid:11229513

Rigate B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86(4):1343-6. https://doi.org/10.1172/JCI114844 PMid:1976655

Pasha MA, Khan AP, Kumar R, Ram RB, Grover SK, Srivastava KK, et al. Variations in angiotensin-converting enzyme gene insertion/deletion polymorphism in Indian populations of different ethnic origins. J Biosci. 2002;27 Suppl 1:67-70. https://doi.org/10.1007/BF02703684 PMid:11927778

Akalin I, Koca E, Karabulut HG, Haznedaroglu IC, Cetiner D, Hayran M, et al. Angiotensin converting enzyme insertion/deletion polymorphisms in leukemic hematopoiesis. Int J Hematol Oncol. 2011;21(1):1-9. https://doi.org/10.4999/uhod.09164

Ladd AM, Vásquez AA, Sayed-Tabatabaei FA, Coebergh JW, Hofman A, Njajou O, et al. Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2143-6.

Elmubarak RA, Babiker AE, Ali EW. Angiotensin converting enzyme I/D polymorphism and risk of acute myeloid leukaemia among sudanese population. LMJ. 2016;2(1):10-4.

Adam AM, Ibrahim KI, Ali EW, Hassan R. Angiotensin converting enzyme insertion/deletion gene polymorphisms in Sudanese patients with chronic lymphocytic leukaemia. Int J Hematol Oncol. 2019;29(1):46-50.

Zmorzynski S, Szudy-Szczyrek A, Popek-Marciniec S, Korszen- Pilecka I, Wojcierowska-Litwin M, Luterek M, et al. ACE insertion/deletion polymorphism (rs4646994) is associated with the increased risk of multiple myeloma. Front Oncol. 2019;9:44. https://doi.org/10.3389/fonc.2019.00044 PMid:30788288

Sugana S, Nandal DH, Kamble S, Bharatha A, Kunkulol R. Genomic DNA isolation from human whole blood samples by non enzymatic salting out method. Int J Pharm Pharmsci. 2014;6:198-9.

Bińkowski J, Miks S. Gene-Calc: Hardy Weinberg equilibrium; 2018. Available from: https://genecalc.pl/hardy-weinberg-page. [Last accessed on 2021 Dec 15].

Uz B, Tatonyan SC, Sayitoglu M, Erbilgin Y, Ng OH, Buyukasik Y, et al. Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders. J Renin Angiotensin Aldosterone Syst. 2013;14(4):308-14. https://doi.org/10.1177/1470320312464677 PMid:23132846

Rezaei RM, Ladmakhi AT. The relationship between INS/DEL of ACE gene and the risk of incidence to lymphoblastic leukaemia by GAP-PCR technique in Iranian population. Egypt Acad J Biol Sci. 2020;12(2):193-99.

Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017;35(9):975-83. https://doi.org/10.1200/JCO.2016.70.7836 PMid:28297628

Hibi S, Goto Y, Ando T, Matsuo K, Wakai K, Tajima K, et al. No association between agiotensin I converting enzyme (ACE) I/D polymorphism and gastric cancer risk among Japanese. Nagoya J Med Sci. 2011;73(3-4):169-75. PMid:21928698

Gsteiger S, Morgenthaler S. Heterogeneity in multistage carcinogenesis and mixture modelling. Theor Biol Med Model. 2008;5:13. https://doi.org/10.1186/1742-4682-5-13 PMid:18644142

Rübben A, Araujo A. Cancer heterogeneity: Converting a limitation into a source of biologic information. J Transl Med. 2017;15(1):190. https://doi.org/10.1186/s12967-017-1290-9 PMid:28886708