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<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2021-7-2-0-2</article-id><article-id pub-id-type="publisher-id">2385</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Association of polymorphism of genes &lt;em&gt;STAT3&lt;/em&gt;, &lt;em&gt;IL10 &lt;/em&gt;and &lt;em&gt;IL12B&lt;/em&gt; with a viral load in women with human papillomavirus&lt;/strong&gt;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Association of polymorphism of genes &lt;em&gt;STAT3&lt;/em&gt;, &lt;em&gt;IL10 &lt;/em&gt;and &lt;em&gt;IL12B&lt;/em&gt; with a viral load in women with human papillomavirus&lt;/strong&gt;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>AlBosal</surname><given-names>Abbas H.H.</given-names></name><name xml:lang="en"><surname>AlBosal</surname><given-names>Abbas H.H.</given-names></name></name-alternatives><email>abbashammadi4@gmail.com</email></contrib></contrib-group><pub-date pub-type="epub"><year>2021</year></pub-date><volume>7</volume><issue>2</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2021/2/Биомед_июнь-12-26.pdf" /><abstract xml:lang="ru"><p>Background:&amp;nbsp;HPV infection leads to an imbalance of pro- and anti-inflammatory cytokines, which contributes to the long-term persistence of the virus in infected cells. The aim of the study:&amp;nbsp;To investigate the association of polymorphisms of genes STAT3 G&amp;gt;C (rs2293152), IL10 -1082 G&amp;gt;A (rs1800896)&amp;nbsp;and IL12B 1188A&amp;gt;C (rs3212227) with a high viral load of human Papillomavirus (HPV), and the influence of gene-gene interactions on the human papillomavirus prolonged infection. Materials and methods:&amp;nbsp;104 women with a high HPV load and 110 healthy women were involved in a case-control study. Genotyping of SNPs for IL10 -1082G&amp;gt;A, IL12B 1188A&amp;gt;C was performed by allele-specific PCR; the rs2293152 STAT3 G&amp;gt;C gene was carried out by restriction fragment length polymorphism (RFLP). Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR) algorithm. Results:&amp;nbsp;The study of single individual SNPs of the STAT3 G&amp;gt;C (rs2293152), IL10 -1082 G&amp;gt;A (rs1800896)&amp;nbsp;and IL12B 1188A&amp;gt;C (rs3212227) genes did not reveal a statistically significant difference in genotypes and alleles frequencies in women with a high HPV load and the control group. The MDR analysis showed a significance of intergenic interactions of the studied loci rs2293152 &amp;ndash; rs1800896 &amp;ndash; rs3212227 for the formation of a high HPV load (OR=2.62, 95%=1.51-4.57, p=0.0006, pbonf =0.002). Conclusion:&amp;nbsp;The interaction of genes STAT3 (rs2293152) &amp;ndash; IL10 (rs1800896) &amp;ndash; IL12B (rs3212227) is associated with the risk of a high HPV load in women. </p></abstract><trans-abstract xml:lang="en"><p>Background:&amp;nbsp;HPV infection leads to an imbalance of pro- and anti-inflammatory cytokines, which contributes to the long-term persistence of the virus in infected cells. The aim of the study:&amp;nbsp;To investigate the association of polymorphisms of genes STAT3 G&amp;gt;C (rs2293152), IL10 -1082 G&amp;gt;A (rs1800896)&amp;nbsp;and IL12B 1188A&amp;gt;C (rs3212227) with a high viral load of human Papillomavirus (HPV), and the influence of gene-gene interactions on the human papillomavirus prolonged infection. Materials and methods:&amp;nbsp;104 women with a high HPV load and 110 healthy women were involved in a case-control study. Genotyping of SNPs for IL10 -1082G&amp;gt;A, IL12B 1188A&amp;gt;C was performed by allele-specific PCR; the rs2293152 STAT3 G&amp;gt;C gene was carried out by restriction fragment length polymorphism (RFLP). Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR) algorithm. Results:&amp;nbsp;The study of single individual SNPs of the STAT3 G&amp;gt;C (rs2293152), IL10 -1082 G&amp;gt;A (rs1800896)&amp;nbsp;and IL12B 1188A&amp;gt;C (rs3212227) genes did not reveal a statistically significant difference in genotypes and alleles frequencies in women with a high HPV load and the control group. The MDR analysis showed a significance of intergenic interactions of the studied loci rs2293152 &amp;ndash; rs1800896 &amp;ndash; rs3212227 for the formation of a high HPV load (OR=2.62, 95%=1.51-4.57, p=0.0006, pbonf =0.002). Conclusion:&amp;nbsp;The interaction of genes STAT3 (rs2293152) &amp;ndash; IL10 (rs1800896) &amp;ndash; IL12B (rs3212227) is associated with the risk of a high HPV load in women. </p></trans-abstract><kwd-group xml:lang="ru"><kwd>human papillomavirus (HPV)</kwd><kwd>cytokines</kwd><kwd>viral load</kwd><kwd>polymorphism</kwd><kwd>STAT3</kwd><kwd>IL10</kwd><kwd>IL12B</kwd></kwd-group><kwd-group xml:lang="en"><kwd>human papillomavirus (HPV)</kwd><kwd>cytokines</kwd><kwd>viral load</kwd><kwd>polymorphism</kwd><kwd>STAT3</kwd><kwd>IL10</kwd><kwd>IL12B</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Chan CK, Aimagambetova G, Ukybassova T, et al. Human Papillomavirus Infection and Cervical Cancer: Epidemiology, Screening, and Vaccination &amp;mdash; Review of Current Perspectives. Journal of Oncology. 2019;2019:3257939. DOI: https://doi.org/10.1155/2019/3257939</mixed-citation></ref><ref id="B2"><mixed-citation>Bruni L, Albero G, Serrano B, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report 17 June 2019 [Internet]. 2019 [cited 2021 Jan 21];22. Available from: https://www.hpvcentre.net/statistics/reports/XWX.pdf.</mixed-citation></ref><ref id="B3"><mixed-citation>Burger EA, Kim JJ, Sy S, et al. Age of Acquiring Causal Human Papillomavirus (HPV) Infections: Leveraging Simulation Models to Explore the Natural History of HPV-induced Cervical Cancer. Clinical Infectious Diseases. 2017;65(6):893-9. DOI: https://doi.org/10.1093/cid/cix475</mixed-citation></ref><ref id="B4"><mixed-citation>Shanmugasundaram S, You J. Targeting Persistent Human Papillomavirus Infection. Viruses. 2017;9(8):229. DOI: https://doi.org/10.3390/v9080229</mixed-citation></ref><ref id="B5"><mixed-citation>Arbyn M, Weiderpass E, Bruni L, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health. 2020;8(2):e191-203. DOI: https://doi.org/10.1016/S2214-109X(19)30482-6</mixed-citation></ref><ref id="B6"><mixed-citation>Li B, Zhang L, Zhao J, et al. The value of cytokine levels in triage and risk prediction for women with persistent high-risk human papilloma virus infection of the cervix. Infectious Agents and Cancer. 2019;14:16. DOI: https://doi.org/10.1186/s13027-019-0231-z</mixed-citation></ref><ref id="B7"><mixed-citation>Fernandes JV, De Medeiros Fernandes TAA, De Azevedo JCV, et al. Link between chronic inflammation and human papillomavirus-induced carcinogenesis (Review). Oncology Letters. 2015;9(3):1015-26. DOI: https://doi.org/10.3892/ol.2015.2884</mixed-citation></ref><ref id="B8"><mixed-citation>Daniilidis A, Koutsos J, Oikonomou Z, et al. Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study. Acta Cytologica. 2016;60:58-64. DOI: https://doi.org/10.1159/000445161</mixed-citation></ref><ref id="B9"><mixed-citation>Woodby B, Scott M, Bodily J. The Interaction Between Human Papillomaviruses and the Stromal Microenvironment. Progress in Molecular Biology and Translational Science. 2016;144:169-238. DOI: https://doi.org/10.1016/bs.pmbts.2016.09.003</mixed-citation></ref><ref id="B10"><mixed-citation>Setrerrahmane S, Xu H. Tumor-related interleukins: old validated targets for new anti-cancer drug development. Molecular Cancer. 2017;16:153. DOI: https://doi.org/10.1186/s12943-017-0721-9</mixed-citation></ref><ref id="B11"><mixed-citation>Lee H, Jeong AJ, Ye S-K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Reports. 2019;52(7):415-23. DOI: https://doi.org/10.5483/BMBRep.2019.52.7.152</mixed-citation></ref><ref id="B12"><mixed-citation>Morgan EL, Wasson CW, Hanson L, et al. STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle. PLoS Pathogens. 2018;14(4):e1006975. DOI: https://doi.org/10.1371/journal.ppat.1006975</mixed-citation></ref><ref id="B13"><mixed-citation>Lin W, Niu Z, Zhang H, et al. Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer. International Journal of Clinical and Experimental Pathology. 2019;12(9): 3604-3612.</mixed-citation></ref><ref id="B14"><mixed-citation>Guadagnin E, Narola J, B&amp;ouml;nnemann CG, et al. Tyrosine 705 Phosphorylation of STAT3 Is Associated with Phenotype Severity in TGF &amp;beta; 1 Transgenic Mice. BioMed Research International. 2015;2015:843743. DOI: https://doi.org/10.1155/2015/843743</mixed-citation></ref><ref id="B15"><mixed-citation>Mitchell RE, Hassan M, Burton BR, et al. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation. Scientific Reports. 2017;7:11315. DOI: https://doi.org/10.1038/s41598-017-11803-y</mixed-citation></ref><ref id="B16"><mixed-citation>Floss DM, Moll JM, Scheller J. IL-12 and IL-23&amp;mdash;Close Relatives with Structural Homologies but Distinct Immunological Functions. Cells. 2020;9(10):2184. DOI: https://doi.org/10.3390/cells9102184</mixed-citation></ref><ref id="B17"><mixed-citation>Berraondo P, Etxeberria I, Ponz-Sarvise M, et al. Revisiting Interleukin-12 as a Cancer Immunotherapy Agent. Clinical Cancer Research. 2018;24(12):2716-8. DOI: https://doi.org/10.1158/1078-0432.CCR-18-0381</mixed-citation></ref><ref id="B18"><mixed-citation>&amp;Aacute;lvarez-Salamero C, Castillo-Gonz&amp;aacute;lez R, Pastor-Fern&amp;aacute;ndez G, et al. IL-23 signaling regulation of pro-inflammatory T-cell migration uncovered by phosphoproteomics. PLoS Biology. 2020;18(3):e3000646. DOI: https://doi.org/10.1371/journal.pbio.3000646</mixed-citation></ref><ref id="B19"><mixed-citation>Alves JJP, Fernandes TAADM, de Araujo JMG, et al. Th17 response in patients with cervical cancer (Review). Oncology Letters. 2018;16(5):6215-27. DOI: https://doi.org/10.3892/ol.2018.9481</mixed-citation></ref><ref id="B20"><mixed-citation>Jang J-P, Baek I-C, Choi E-J, et al. Multiplex Genotyping of Cytokine Gene SNPs Using Fluorescence Bead Array. PLoS ONE. 2015;10(2):e0118008. DOI: https://doi.org/10.1371/journal.pone.0118008</mixed-citation></ref><ref id="B21"><mixed-citation>Guo Y, Jamison DC. The distribution of SNPs in human gene regulatory regions. BMC Genomics. 2005;6:140. DOI: https://doi.org/10.1186/1471-2164-6-140</mixed-citation></ref><ref id="B22"><mixed-citation>Kirchner S, Cai Z, Rauscher R, et al. Alteration of protein function by a silent polymorphism linked to tRNA abundance. PLoS Biology. 2017;15(5):e2000779. DOI: https://doi.org/10.1371/journal.pbio.2000779</mixed-citation></ref><ref id="B23"><mixed-citation>Lesiak A, Zakrzewski M, Przybyłowska K, et al. Atopic dermatitis patients carrying G allele in &amp;ndash;1082 G/A IL-10 polymorphism are predisposed to higher serum concentration of IL-10. Archives of Medical Science. 2014;10(6):1239-43. DOI: https://doi.org/10.5114/aoms.2014.47833</mixed-citation></ref><ref id="B24"><mixed-citation>Hoffmann TW, Halimi J-M, B&amp;uuml;chler M, et al. Impact of a Polymorphism in the IL-12p40 Gene on the Outcome of Kidney Transplantation. Transplantation Proceedings. 2009;41(2):654-6. DOI: https://doi.org/10.1016/j.transproceed.2008.12.002</mixed-citation></ref><ref id="B25"><mixed-citation>Shi X, Jia Y, Xie X, et al. Single-nucleotide polymorphisms of the IL-12 gene lead to a higher cancer risk: a meta-analysis based on 22,670 subjects. Genes and Genetic Systems. 2017;92(4):173-87. DOI: https://doi.org/10.1266/ggs.16-00024</mixed-citation></ref><ref id="B26"><mixed-citation>Doorbar J, Egawa N, Griffin H, et al. Human papillomavirus molecular biology and disease association. Reviews in Medical Virology. 2015;25(51):2-23. DOI: https://doi.org/10.1002/rmv.1822</mixed-citation></ref><ref id="B27"><mixed-citation>Obeid DA, Almatrrouk SA, Khayat HH, et al. Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia. Heliyon. 2020;6(2):e03473. DOI: https://doi.org/10.1016/j.heliyon.2020.e03473</mixed-citation></ref><ref id="B28"><mixed-citation>Gupta SM, Mania-Pramanik J. Retraction Note: Molecular mechanisms in progression of HPV-associated cervical carcinogenesis. Journal of Biomedical Science. 2019;26:28. DOI: https://doi.org/10.1186/s12929-019-0520-2</mixed-citation></ref><ref id="B29"><mixed-citation>Shen YY, Du H, Liu ZH, et al. The relationship between the human papillomavirus viral load and the degree of pathology in the cervical intraepithelial neoplasia. Chinese Journal of Clinical Obstetrics and Gynecology. 2017;18(4):313-316.</mixed-citation></ref><ref id="B30"><mixed-citation>Del R&amp;iacute;o-Ospina L, Soto-De Le&amp;oacute;n SC, Camargo M, et al. The DNA load of six high-risk human papillomavirus types and its association with cervical lesions. BMC Cancer. 2015;15:100. DOI: https://doi.org/10.1186/s12885-015-1126-z</mixed-citation></ref><ref id="B31"><mixed-citation>Morgan EL, Macdonald A. Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1&amp;mdash;NF&amp;kappa;B&amp;mdash;IL-6 signalling axis. PLoS Pathogens. 2019;15(6):e1007835. DOI: https://doi.org/10.1371/journal.ppat.1007835</mixed-citation></ref><ref id="B32"><mixed-citation>Walch-R&amp;uuml;ckheim B, Pahne-Zeppenfeld J, Fischbach J, et al. STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs. Cancer Research. 2016;76(13):3872-83. DOI: https://doi.org/10.1158/0008-5472.CAN-14-1306</mixed-citation></ref><ref id="B33"><mixed-citation>Zyuzkov GN, Udut EV, Miroshnichenko LA, et al. The specific role of JAK / STAT3-signaling in the regulation of the functions of mesenchymal progenitor cells. Bulletin of Experimental Biology and Medicine. 2017;164(9):294-7. Russian.</mixed-citation></ref><ref id="B34"><mixed-citation>Morgan EL, Macdonald A. Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies. Viruses. 2020;12(9):977. DOI: https://doi.org/10.3390/v12090977</mixed-citation></ref><ref id="B35"><mixed-citation>Yan R, Lin F, Hu C, et al. Association between STAT3 polymorphisms and cancer risk: a meta-analysis. Molecular Genetics and Genomics. 2015;290:2261-70. DOI: https://doi.org/10.1007/s00438-015-1074-y</mixed-citation></ref><ref id="B36"><mixed-citation>Rojas JM, Avia M, Mart&amp;iacute;n V, et al. IL-10: a multifunctional cytokine in viral infections. Journal of Immunology Research. 2017;2017:6104054. DOI: https://doi.org/10.1155/2017/6104054</mixed-citation></ref><ref id="B37"><mixed-citation>Wang B, Wang H, Li P, et al. Relationships of interleukin-10 with the regulatory T cell ratio and prognosis of cervical cancer patients. Clinics. 2018;73. DOI: https://doi.org/10.6061/clinics/2018/e679</mixed-citation></ref><ref id="B38"><mixed-citation>Larsson L, Johansson P, Jansson A, et al. The Sp1 transcription factor binds to the G-allele of the &amp;ndash;1087 IL-10 gene polymorphism and enhances transcriptional activation. Genes and Immunity. 2009;10:280-4. DOI: 1 https://doi.org/10.1038/gene.2008.79</mixed-citation></ref><ref id="B39"><mixed-citation>Farzaneh F, Roberts SA, Mandal D, et al. The IL-10 &amp;minus;1082G polymorphism is associated with clearance of HPV infection. BJOG: An International Journal of Obstetrics and Gynaecology. 2006;113(8):961-4. DOI: https://doi.org/10.1111/j.1471-0528.2006.00956.x</mixed-citation></ref><ref id="B40"><mixed-citation>Chagas BS, de Lima RCP, J&amp;uacute;nior SSLP, et al. Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus. Cytokine. 2019;113:99-104. DOI: https://doi.org/10.1016/j.cyto.2018.06.014</mixed-citation></ref><ref id="B41"><mixed-citation>Zeng YY, Chen XY, Tian KG, et al. The correlation of interleukin-10 gene polymorphism and HPV infection and cervical lesions in Dongguan region. Journal of Clinical and Experimental Medicine. 2015;14:636-639.</mixed-citation></ref><ref id="B42"><mixed-citation>Datta A, Zahora FT, Aziz MA, et al. Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women. International Immunopharmacology. 2020;89(B):107091. DOI: https://doi.org/10.1016/j.intimp.2020.107091</mixed-citation></ref><ref id="B43"><mixed-citation>Tugues S, Burkhard SH, Ohs I, et al. New insights into IL-12-mediated tumor suppression. Cell Death and Differentiation. 2015;22:237-46. DOI: https://doi.org/10.1038/cdd.2014.134</mixed-citation></ref><ref id="B44"><mixed-citation>Yan J, Smyth MJ, Teng MWL. Interleukin (IL)-12 and IL-23 and Their Conflicting Roles in Cancer. Cold Spring Harbor perspectives in biology. 2018;10:a028530. DOI: https://doi.org/10.1101/cshperspect.a028530</mixed-citation></ref><ref id="B45"><mixed-citation>R&amp;eacute;b&amp;eacute; C, Ghiringhelli F. STAT3, a Master Regulator of Anti-Tumor Immune Response. Cancers (Basel). 2019;11(9):1280. DOI: https://doi.org/10.3390/cancers11091280</mixed-citation></ref><ref id="B46"><mixed-citation>Morahan G, Huang D, Ymer SI, et al. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nature Genetics. 2001;27:218-21. DOI: https://doi.org/10.1038/84872</mixed-citation></ref><ref id="B47"><mixed-citation>Schurich A, Raine C, Morris V, et al. The role of IL-12/23 in T cell&amp;ndash;related chronic inflammation: implications of immunodeficiency and therapeutic blockade. Rheumatology. 2018;57(2):246-54. DOI: https://doi.org/10.1093/rheumatology/kex186</mixed-citation></ref><ref id="B48"><mixed-citation>Han S-S, Cho E-Y, Lee TS, et al. Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical caner in Korean women. European Journal of Obstetrics &amp;amp; Gynecology and Reproductive Biology. 2008;140(1):71-5. DOI: https://doi.org/10.1016/j.ejogrb.2008.02.007</mixed-citation></ref><ref id="B49"><mixed-citation>Tamandani DMK, Shekari M, Suri V. Interleukin-12 Gene Polymorphism and Cervical Cancer Risk. American Journal of Clinical Oncology. 2009;32(5):524-8. DOI: https://doi.org/10.1097/COC.0b013e318192519a</mixed-citation></ref><ref id="B50"><mixed-citation>Roszak A, Mostowska A, Sowińska A, et al. Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer. Pathology and Oncology Research. 2012;18:997-1002. DOI: https://doi.org/10.1007/s12253-012-9532-x</mixed-citation></ref><ref id="B51"><mixed-citation>Ram&amp;iacute;rez-Bello J, Jim&amp;eacute;nez-Morales M. Functional implications of single nucleotide polymorphisms (SNPs) in protein-coding and non-coding RNA genes in multifactorial diseases. Gaceta Medica de Mexico. 2017;153:238-50.</mixed-citation></ref><ref id="B52"><mixed-citation>Wang K, Zhou B, Zhang J, et al. Association of Signal Transducer and Activator of Transcription 3 Gene Polymorphisms with Cervical Cancer in Chinese Women. DNA and Cell Biology. 2011;30(11):931-6. DOI: https://doi.org/10.1089/dna.2010.1179</mixed-citation></ref><ref id="B53"><mixed-citation>Guti&amp;eacute;rrez-Hoya A, Soto-Cruz I. Role of the JAK/STAT Pathway in Cervical Cancer: Its Relationship with HPV E6/E7 Oncoproteins. Cells. 2020;9(10):2297. DOI: https://doi.org/10.3390/cells9102297</mixed-citation></ref></ref-list></back></article>