Association between IL1R1 rs2234650 Polymorphism in Patients with Acute Lymphoblastic Leukemia Infected with HHV-6A
DOI:
https://doi.org/10.54133/ajms.v8i2.1705Keywords:
Acute lymphoblastic leukemia, Human herpesvirus 6-A, Interleukin-1 receptor type 1, rs2234650, PCR, SequencingAbstract
Background: Everyone contracts the common infection known as human herpesvirus 6 (HHV-6). Particularly associated with encephalitis, human herpesvirus 6B (HHV-6B) poses a risk of morbidity and death to recipients of allogeneic hematopoietic stem cell transplants. IL-1β and interleukin-1α (IL-1α) are critical for enhancing infection resistance. Objective: To ascertain whether HHV-6A and the IL1R1 rs2234650 gene polymorphism are related and could be risk factors for Iraqi infants developing acute lymphoblastic leukemia (ALL). Methods: This case-control study included 150 blood samples from 100 patients diagnosed with ALL and 50 from healthy subjects. The IL1R1 rs2234650 gene polymorphism was identified using the Sanger sequencing method, and HHV-6A using PCR. Results: Age group and sex were found to differ significantly. Of 100 samples, 32 percent had HHV6A. The polymorphism of the IL-1R1 rs2234650 gene revealed that the distribution of DNA polymorphisms according to C\C, C\G, G\G, C\T, T\T, and G\T was 30%, 28%, 16%, 8%, 6%, and 12%, respectively, in patients with ALL and 33.33%, 26.67%, and 16.67%, respectively. 3.33%, 13.33%, and 6.67% in the group that was deemed to be in apparently healthy control (AHC). The frequency of the polymorphism's genotype distribution varied significantly between the patient and control groups. Conclusions: HHV6A and IL1R1 rs2234650 polymorphisms of ALL variations may be risk factors in the pathophysiology of ALL in Iraqi children.
Downloads
References
Caselli E, D'Accolti M, Caccuri F, Soffritti I, Gentili V, Bortolotti D, et al. The U94 gene of human herpesvirus 6: A narrative review of its role and potential functions. Cells. 2020;9(12):2608. doi: 10.3390/cells9122608. DOI: https://doi.org/10.3390/cells9122608
Katia P, Luisa S , Antonio P, Jaime V , Ilaria C , Maria S, et al. High incidence of early human herpesvirus-6 infection in children undergoing haploidentical manipulated stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2018;24(12):2549-2557. doi: 10.1016/j.bbmt.2018.07.033. DOI: https://doi.org/10.1016/j.bbmt.2018.07.033
Gabrielli L, Balboni A, Borgatti EC, Virgili G, Petrisli E, Cantiani A, et al. Inherited chromosomally integrated human herpesvirus 6: Laboratory and clinical features. Microorganisms. 2023;11(3):548. doi: 10.3390/microorganisms11030548. DOI: https://doi.org/10.3390/microorganisms11030548
Aimola G, Wight DJ, Flamand L, Kaufer BB. Excision of integrated human herpesvirus 6A genomes using CRISPR/Cas9 technology. Microbiol Spectr. 2023;11(2):e0076423. doi: 10.1128/spectrum.00764-23. DOI: https://doi.org/10.1128/spectrum.00764-23
Tatiana I. Lobanova, Dmitry S. Tikhomirov, Olga A. Gavrilina, et al. Human herpesvirus 6 infection in immunocompromised patients after chemotherapy and autologous stem cell transplantation. Blood. 2017;130(1):1013. doi: 10.1182/blood.V130.Suppl_1.1013.1013.
Kampouri E, Handley G, Hill JA. Human herpes virus-6 (HHV-6) reactivation after hematopoietic cell transplant and chimeric antigen receptor (CAR)-T cell therapy: A shifting landscape. Viruses. 2024;16(4):498. doi: 10.3390/v16040498. DOI: https://doi.org/10.3390/v16040498
Noviello M, Lorentino F, Xue E, Racca S, Furnari G, Valtolina V, et al. Human herpesvirus 6-specific T-cell immunity in allogeneic hematopoietic stem cell transplant recipients. Blood Adv. 2023;7(18):5446-5457. doi: 10.1182/bloodadvances.2022009274. DOI: https://doi.org/10.1182/bloodadvances.2022009274
Wang F, Chi J, Peng G, Zhou F, Wang J, Li L, et al. Development of virus-specific CD4+ and CD8+ regulatory T cells induced by human herpesvirus 6 infection. J Virol. 2014;88(2):1011-1024. doi: 10.1128/JVI.02586-13. DOI: https://doi.org/10.1128/JVI.02586-13
Schwarz CM, Strenger V, Strohmaier H, Singer G, Kaiser M, Raicht A, et al. HHV-6 specific T-cell Immunity in healthy children and adolescents. Front Pediatr. 2018;6:191. doi: 10.3389/fped.2018.00191. DOI: https://doi.org/10.3389/fped.2018.00191
Eliassen E, Lum E, Pritchett J, Ongradi J, Krueger G, Crawford JR, et al. Human herpesvirus 6 and malignancy: A review. Front Oncol. 2018;13(8):512. doi: 10.3389/fonc.2018.00512. DOI: https://doi.org/10.3389/fonc.2018.00512
de Mooij CEM, Netea MG, van der Velden WJFM, Blijlevens NMA. Targeting the interleukin-1 pathway in patients with hematological disorders. Blood. 2017;129(24):3155-3164. doi: 10.1182/blood-2016-12-754994. DOI: https://doi.org/10.1182/blood-2016-12-754994
Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. doi: 10.1111/imr.12621. DOI: https://doi.org/10.1111/imr.12621
Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J. The role of interleukin-1 in general pathology. Inflamm Regen. 2019;39:12. doi: 10.1186/s41232-019-0101-5. DOI: https://doi.org/10.1186/s41232-019-0101-5
Faten N, Agnès GD, Nadia BF, Nabil AB, Monia Z, Abderrahim K, et al. Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study. Infect Agent Cancer. 2012;7(1):31. doi: 10.1186/1750-9378-7-31. DOI: https://doi.org/10.1186/1750-9378-7-31
Nefzi F, Abid Ben Salem N, Khelif A, Feki S, Aouni M, Gautheret-Dejean A. Quantitative analysis of human herpesvirus-6 and human cytomegalovirus in blood and saliva from patients with acute leukemia. J Med Virol. 2015;87(3):451-460. doi: 10.1002/jmv.24059. DOI: https://doi.org/10.1002/jmv.24059
Kozireva S, Nemceva G, Danilane I, Pavlova O, Blomberg J, Murovska M. Prevalence of blood-borne viral infections (cytomegalovirus, human herpesvirus-6, human herpesvirus-7, human herpesvirus-8, human T-cell lymphotropic virus-I/II, human retrovirus-5) among blood donors in Latvia. Ann Hematol. 2001;80(11):669-673. doi: 10.1007/s002770100359. DOI: https://doi.org/10.1007/s002770100359
Géraudie B, Charrier M, Bonnafous P, Heurté D, Desmonet M, Bartoletti MA, et al. Quantitation of human herpesvirus-6A, −6B and −7 DNAs in whole blood, mononuclear and polymorphonuclear cell fractions from healthy blood donors. J Clin Virol. 2012;53(2):151-155. doi: 10.1016/j.jcv.2011.10.017. DOI: https://doi.org/10.1016/j.jcv.2011.10.017
Boutolleau D, Bonduelle O, Sabard A, Devers L, Agut H, Gautheret-Dejean A. Detection of human herpesvirus 7 DNA in peripheral blood reflects mainly CD4+ cell count in patients infected with HIV. J Med Virol. 2005;76(2):223-228. doi: 10.1002/jmv.20345. DOI: https://doi.org/10.1002/jmv.20345
Gravel A, Sinnett D, Flamand L. Frequency of chromosomally integrated human herpesvirus 6 in children with acute lymphoblastic leukemia. PLoS One. 2013;8(12):e84322. doi: 10.1371/journal.pone.0084322. DOI: https://doi.org/10.1371/journal.pone.0084322
Elisa S, Bérénice C, Agnès G, Paola B. Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia. J Med Virol. 2008;80(4):689-693. doi: 10.1002/jmv.21118. DOI: https://doi.org/10.1002/jmv.21118
Kano Y, Inaoka M, Shiohara T. Association between anticonvulsant hypersensitivity syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia. Arch Dermatol. 2004;140(2):183–188. doi: 10.1001/archderm.140.2.183. DOI: https://doi.org/10.1001/archderm.140.2.183
Luppi M, Barozzi P, Bosco R, Vallerini D, Potenza L, Forghieri F, et al. Human herpesvirus 6 latency characterized by high viral load: chromosomal integration in many, but not all, cells. J Infect Dis. 2006;194(7):1020-1021; doi: 10.1086/506952. DOI: https://doi.org/10.1086/506952
Sester M, Sester U, Gärtner B, Heine G, Girndt M, Mueller-Lantzsch N, et al. Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation. Transplantation. 2001;71(9):1287-1294. doi: 10.1097/00007890-200105150-00018. DOI: https://doi.org/10.1097/00007890-200105150-00018
Nastke MD, Becerra A, Yin L, Dominguez-Amorocho O, Gibson L, Stern LJ, et al. Human CD4+ T cell response to human herpesvirus 6. J Virol. 2012;86(9):4776–4792. doi: 10.1128/JVI.06573-11. DOI: https://doi.org/10.1128/JVI.06573-11
Tejada-Simon MV, Zang YC, Hong J, Rivera VM, Killian JM, Zhang JZ. Detection of viral DNA and immune responses to the human herpesvirus 6 101-kilodalton virion protein in patients with multiple sclerosis and in controls. J Virol. 2002;76(12):6147-6154. doi: 10.1128/jvi.76.12.6147-6154.2002. DOI: https://doi.org/10.1128/JVI.76.12.6147-6154.2002
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008. doi: 10.3390/ijms20236008. DOI: https://doi.org/10.3390/ijms20236008
Witkin SS, Santosh V,Yih M, Kunihiko D, Bongiovanni AM, Stefan G. Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1β and interleukin-1 receptor antagonist and pregnancy outcome. Am J Obstetr Gynecol. 2003;189(5):1413-1417. doi: 10.1067/s0002-9378(03)00630-6. DOI: https://doi.org/10.1067/S0002-9378(03)00630-6
Yadav DK, Tripathi AK, Gupta D, Shukla S, Singh AK, Kumar A, et al. Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia. Blood Res. 2017;52(4):264-269. doi: 10.5045/br.2017.52.4.264. DOI: https://doi.org/10.5045/br.2017.52.4.264
Zapata TM, Arredondo GJL, Rivera-Luna R, Klünder KM, Mancilla RJ, Sánchez UR, et al. Interleukin-1 receptor antagonist gene polymorphism increases susceptibility to septic shock in children with acute lymphoblastic leukemia. Pediatr Infect Dis J. 2013;32(2):136-139. doi: 10.1097/INF.0b013e31827566dd. DOI: https://doi.org/10.1097/INF.0b013e31827566dd
Al-Tawil MM, Kamal TM, Borham OM, Abd El-Ghany SM. Interleukin-1 receptor antagonist gene polymorphisms in Egyptian children and adolescents with primary immune thrombocytopenia: association with disease susceptibility, response to therapy, and outcome. J Pediatr Hematol Oncol. 2023;45:e650–654. doi: 10.1097/MPH.0000000000002570. DOI: https://doi.org/10.1097/MPH.0000000000002570
El Amawy M, Shahin E. Assessment of IL-1B31 and IL RA gene polymorphism in immune thrombocytopenia. Benha Med J. 2023;40:298–309. doi: 10.21608/BMFJ.2023.161067.1659. DOI: https://doi.org/10.21608/bmfj.2023.161067.1659
Elsaadany ZA, Momen NN, Elmesawy OE, Abd Elhady M, Gad A. Studying the role of IL-1B genetic polymorphisms in the development of primary immune thrombocytopenia among Egyptian children. Gene Rep. 2023;30:101736. doi: 10.1016/j.genrep.2022.101736. DOI: https://doi.org/10.1016/j.genrep.2022.101736
Wahlund M, Appell ML, Myrberg IH , Berggren A, Nilsson A . Genetic sequence variants in TLR4, MBL or IL-1 Receptor antagonist is not associated with increased risk for febrile neutropenia in children with ALL. Children. 2020;7(12):296. doi: 10.3390/children7120296. DOI: https://doi.org/10.3390/children7120296

Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 )

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Published by Al-Rafidain University College. This is an open access journal issued under the CC BY-NC-SA 4.0 license (https://creativecommons.org/licenses/by-nc-sa/4.0/).