Login Register Cart 0
Research Article

ARV相关肝毒性中白细胞介素-2（330 G / T）启动子多态性的发生

卷 19, 期 3, 2019

页: [206 - 215] 页: 10

弟呕挨: 10.2174/1566524019666190411093451

价格: $65

摘要

背景：IL-2细胞因子参与HIV复制，并且还已知会引起肝损伤。 IL-2基因中的多态性与白细胞介素-2产生的改变有关。 方法：因此，我们使用PCR-RFLP方法评估了165名HIV患者（34名患者和131名无肝毒性患者）和155名健康对照者中IL-2-303G / T多态性的患病率。 结果：在肝毒性患者中，IL-2-303GT，-303GT + TT基因型与无肝毒性和健康对照相比较不普遍（29.4％对42.7％，58.8％对69.5％; 29.4％对40.6％） ，分别为58.8％和66.5％。在使用烟草和酒精的肝毒性患者中，IL-2-303GT，-303TT基因型与非使用者相比分布较高（42.9％对25.9％，OR = 8.52,42.9％对25.9％，OR = 9.09，和28.6％对比29.6％，OR = 1.63,42.9％对25.9％，OR = 2.93），而IL-2-303TT基因型在饮酒的HIV患者中更常发生（34.1％对23.0％）。与efavirenz相比，具有肝毒性的奈韦拉平使用者代表IL-2-303GT，-303TT基因型（34.8％对18.2％，OR = 4.64,34.8％对18.2％，OR = 3.88）。在奈韦拉平使用者中，IL-2-303GT基因型与获得肝毒性的易感性相关，具有临界意义（OR = 4.24，P = 0.06）。使用奈韦拉平的HIV患者主要代表IL-2-303TT基因型（26.9％对25.0％，OR = 2.35），而使用奈韦拉平+酒精的HIV患者以更高的频率呈现IL-2 -330TT基因型（34.2 %% vs .23.5％，OR = 1.51）。在使用奈韦拉平+酒精的肝毒性患者中，基因型IL-2 - 330TT占优势（60.0％对27.8％，OR = 3.16）。 结论：因此，IL-2-303G / T多态性不能赋予ARV相关肝毒性的易感性。然而，使用奈韦拉平的IL-2-303G / T多态性可能有助于获得ARV相关肝毒性的风险。

关键词: IL-2基因，遗传多态性，ARV相关肝毒性，HIV患者，NNRTI方案，细胞因子。

« Previous Next »
[1]
McGovern B. Hepatic safety and HAART. J Int Assoc Physicians AIDS Care (Chic) 2004; 3(2): S24-40.
[2]
Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 2006; 1: 23-61.
[3]
Heim MH, Thimme R. Innate and adaptive immune responses in HCV infections. J Hepatol 2014; 61(1)(Suppl.): 4-25.
[4]
Reisler R, Servoss J, Sherman K. Incidence of hepatotoxicity and mortality in 21 adult antiretroviral treatment trials. 1st IAS Conference on HIV Pathogenesis and Treatment. Buenos Aires. 2001.
[5]
Nagpal M, Tayal V, Kumar S, Gupta U. Adverse drug reactions to antiretroviral therapy in AIDS patients at a tertiary care hospital in India: A prospective observational study. Indian J Med Sci 2010; 64: 245-52.
[6]
Albanidou-Farmaki E, Markopoulos AK, Kalogerakou F, Antoniades DZ. Detection, enumeration and characterization of The percells secreting type1 and type2 cytokines in patients with recurrent aphthous stomatitis. Tohoku J Exp Med 2007; 212(2): 101-5.
[7]
Chavan M, Jain H, Diwan N, Khedkar S, Shete A, Durkar S. Recurrentaphthous stomatitis: A review. J Oral Pathol Med 2012; 41(8): 577-83.
[8]
Morgan ET. Regulation of cytochrome P450 by inflammatory mediators: why and how? Drug Metab Dispos 2001; 29(6): 207-12.
[9]
Aitken AE, Richardson TA, Morgan ET. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 2006; 46: 123-49.
[10]
Elkahwaji J, Robin MA, Berson A, et al. Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy. Biochem Pharmacol 1999; 57(8): 951-4.
[11]
Togawa S, Joh T, Itoh M, et al. Interleukin-2 gene polymorphisms associated with increased risk of gastricatrophy from Helicobacter pylori infection. Helicobacter 2005; 10(3): 172-8.
[12]
Matesanz F, Delgado C, Fresno M, Alcina A. Allelic selection of human IL-2 gene. Eur J Immunol 2000; 30(12): 3516-21.
[13]
Matesanz F, Delgado C, Fresno M, Alcina A. Two regions within the human IL-2 gene promoter are important for inducible IL-2 expression. J Immunol 1988; 141(12): 662-6.
[14]
John S, Turner D, Donn R, et al. Two novel biallelic polymorphisms in the IL-2 gene. Eur J Immunogenet 1998; 25(6): 419-20.
[15]
Al-Qahtani A, Al-Anazi M, Abdo AA, et al. Correlation between genetic variations and serum level of interleukin 28B with virus genotypes and disease progression in chronic hepatitis-C virus infection. J Immunol Res 2015; 2015768470
[16]
Zhang L, Miao L, Han F, Dou XG. Cytokine levels in serum of patients with chronic hepatitis C and its significance. Xi Bao Yu Fen ZiMian Yi XueZaZhi 2011; 27(3): 301-3.
[17]
van Manen D, Delaneau O, Kootstra NA, et al. Genome-wide associations can in HIV-1-infected individuals identifying variants influencing disease course. PLoS One 2011; 6(7)e22208
[18]
Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother 2001; 12(3): 133-50.
[19]
Kreuzer KA, Dayer JM, Rockstroh JK, et al. The IL-1 system in HIV infection: peripheral concentrations of IL-1beta, IL-1 receptor antagonist and soluble IL-1 receptor type II. Clin Exp Immunol 1997; 109(1): 54-8.
[20]
Gao QJ, Liu DW, Zhang SY, et al. Polymorphisms of some cytokines and chronic hepatitis B and C virus infection. World J Gastroenterol 2009; 15(44): 5610-9.
[21]
Shen Y, Liu Y, Liu S, Zhang A. The association between -330T/G polymorphism of interleukin-2 gene and bladder cancer. DNA Cell Biol 2012; 31(6): 983-7.
[22]
Song H, Chen L, Cha Z, Bai J. Interleukin 2 gene polymorphisms are associated with non-Hodgkin lymphoma. DNA Cell Biol 2012; 31(7): 1279-84.
[23]
Wei YS, Lan Y, Zhang L, Wang JC. Association of the interleukin-2 polymorphisms with interleukin-2 serum levels and risk of nasopharyngeal carcinoma. DNA Cell Biol 2010; 29(7): 363-8.
[24]
Amirzargar AA, Bagheri M, Ghavamzadeh A, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet 2005; 32(3): 167-71.
[25]
Shin WG, Jang JS, Kim HS, et al. Polymorphisms of interleukin-1 and interleukin-2 genes in patients with gastric cancer in Korea. J Gastroenterol Hepatol 2008; 23(10): 1567-73.
[26]
Wu J, Lu Y, Ding YB, et al. Promoter polymorphisms of IL2, IL4, and risk of gastric cancer in a high-risk Chinese population. Mol Carcinog 2009; 48(7): 626-32.
[27]
Hu XB, Ouyang LZ, Tang LL. Interleukin-2 gene polymorphisms and prognosis of breast cancer. Genet Test Mol Biomarkers 2013; 17(6): 453-7.
[28]
Song H, Chen L, Cha Z, Bai J. Interleukin 2 gene polymorphisms are associated with non-Hodgkin lymphoma. DNA Cell Biol 2012; 31(7): 1279-84.
[29]
Berković MC, Jokić M, Marout J, Radosević S, Zjacić-Rotkvić V, Kapitanović S. IL-2 -330T/GSNP and serum values-potential new tumor markers in neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NETs). J Mol Med (Berl) 2010; 88(4): 423-9.
[30]
Savage SA, Abnet CC, Haque K, et al. Polymorphisms in interleukin-2, -6, and -10 are not associated with gastric cardia or esophageal cancer in a high-risk chinese population. Cancer Epidemiol Biomarkers Prev 2004; 13(9): 1547-9.
[31]
Peng Q, Li H, Lao X, et al. Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population. Infect Genet Evol 2014; 27: 375-81.
[32]
Bei CH, Bai H, Yu HP, et al. Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepato-cellular carcinoma risk in Southern Guangxi, China. Asian Pac J Cancer Prev 2014; 15(16): 6961-7.
[33]
López RV, Zago MA, Eluf-Neto J, et al. Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer. Braz J Med Biol Res 2011; 44(10): 1006-12.
[34]
Seder RA. Acquisition of lymphokine-producing phenotype by CD4+ T cells. J Allergy Clin Immunol 1994; 94(6 Pt 2): 1195-202.
[35]
Dragani TA. Risk of HCC: genetic heterogeneity and complex genetics. J Hepatol 2010; 52(2): 252-7.
[36]
Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, et al. Esophageal and gastric cardia cancer risk and folate- and vitamin B (12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev 2003; 12(11 Pt 1): 1222-6.
[37]
Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol 2010; 4(3): 174-91.
[38]
Jarmalaite S, Andrekute R, Scesnaite A, et al. Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study. J Cancer Res Clin Oncol 2010; 136(6): 847-54.
[39]
Pawlik A, Kurzawski M, Florczak M, Gawronska Szklarz B, Herczyńska M. IL1beta+3953 exon 5 and IL-2 -330 promoter polymorphisms in patients with rheumatoid arthritis. Clin Exp Rheumatol 2005; 23(2): 159-64.
[40]
Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12(12): 1365-71.
[41]
Haynes BF. Gut microbes out of control in HIV infection. Nat Med 2006; 12(12): 1351-2.
[42]
Hoffmann SC, Stanley EM, Darrin Cox E, Craighead N, DiMercurio BS, Koziol DE, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 2001; 72: 1444-50.
[43]
Singh H, Lata S, Dhole TN, Gangakhedkar RR. Occurrence of CYP2B6 516G>T polymorphism in patients with ARV-associated hepatotoxicity. Mol Genet Genomic Med 2019; 7(4)e598
[44]
Vento S, Garofano T, Renzini C, Casali F, Ferraro T, Concia E. Enhancement of hepatitis C virus replication and liver damage in HIV co-infected patients on antiretroviral combination therapy. AIDS 1998; 12(1): 116-7.
[45]
Savès M, Raffi F, Clevenbergh P, et al. Hepatitis B or hepatitis C virus infection is a risk factor for severe hepatic cytolysis after initiation of a protease inhibitor-containing antiretroviral regimen in human immunodeficiency virus-infected patients. The Aproco Study Group. Antimicrob Agents Chemother 2000; 44(12): 3451-5.
[46]
Kaplowitz N. Biochemical and cellular mechanisms of toxic liver injury. Semin Liver Dis 2002; 22(2): 137-44.
[47]
Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology 2006; 43(2)(Suppl. 1): S54-62.
[48]
Bagheri M, Omrani D, Abdi-Rad I. Cytokine single nucleotide polymorphisms in Iran. J Interferon Cytokine Res 2006; 26: 414-20.
[49]
Manchanda PK, Kumar A, Sharma RK, Goel H, Mittal RD. Association of pro/anti-inflammatory cytokine gene variants in renal transplant patients with allograft outcome and cyclosporine immunosuppressant levels. Biologics 2008; 2(4): 875-84.
[50]
Sivangala R, Ponnana M, et al. Association of cytokine gene polymorphisms in patients with tuberculosis and their household contacts. Scand J Immunol 2014; 79(3): 197-205.
[51]
Najafi S, Yousefi H, Mohammadzadeh M, et al. Interleukin-2, Interferon-gamma Gene Polymorphisms in Recurrent Aphthous Stomatitis. Prague Med Rep 2017; 118(2-3): 81-6.
[52]
Song N, Han S, Lee KM, et al. Genetic variants in interleukin-2 and risk of lymphoma among children in Korea. Asian Pac J Cancer Prev 2012; 13(2): 621-3.
[53]
Shen Y, Liu Y, Liu S, Zhang A. The association between -330T/G polymorphism of interleukin2gene and bladder cancer. DNA Cell Biol 2012; 31(6): 983-7.
[54]
Wei YS, Lan Y, Zhang L, Wang JC. Association of the interleukin-2 polymorphisms with interleukin-2 serum levels and risk of nasopharyngeal carcinoma. DNA Cell Biol 2010; 29(7): 363-8.
[55]
Feldman JG, Minkoff H, Schneider MF, et al. Association of cigarette smoking with HIV prognosis among women in the HAART era: a report from the women’s interagency HIV study. Am J Public Health 2006; 96(6): 1060-5.
[56]
Okuda M, Li K, Beard MR, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002; 122(2): 366-75.
[57]
Fauci AS. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science 1993; 262(5136): 1011-8.
[58]
Bagheri M, Abdi-Rad I, Omrani D, Khalkhali HR. Heterogeneity of cytokine single-nucleotide polymorphisms among the Iranian and in the other East-South Asian populations. Transfus Med 2006; 16(3): 192-9.

Rights & Permissions Print Cite
Article Metrics
19
2
© 2024 Bentham Science Publishers | Privacy Policy