Aim: This study aimed to evaluate rs1179251 single nucleotide polymorphism in the IL-22 gene as a host factor and its effect on chronic hepatitis B infection.
Background: Interleukin 22 (IL-22) belongs to a group of recently discovered cytokines, and it is produced and secreted by innate lymphoid cells (ILCs) and T helper 22 (Th22) cells. This cytokine plays dual roles as pro-inflammatory and anti-inflammatory effects in various conditions and different tissues of the body.
Methods: This study was performed based on a case-control format to assess IL-22 rs1179251 single nucleotide polymorphism genotypic and allelic frequencies among 227 hepatitis B chronic patients and 227 healthy controls. The polymerase chain reaction and restriction fragment length polymorphism techniques were employed to determine the polymorphism’s genotypes.
Results: Genotypes Frequencies in patients’ group were determined CC 59.91%, CG 37.89%, and GG 2.20% respectively in comparison to CC 63.44%, CG 31.72% and GG 4.85% in control group. The findings revealed that there was no statistically significant difference in the genotypes (P=0.156) frequencies of IL-22 gene polymorphism (rs1179251) between patients and control groups.
Conclusion: No association was found between rs1179251 single nucleotide polymorphism in IL-22 gene and chronic hepatitis B infection. So, in spite of the importance of IL-22 gene in immune responses, the studied polymorphism does not serve a decisive role in susceptibility to hepatitis B virus chronic infection.
Keywords: Interleukin 22, Single nucleotide polymorphism, Hepatitis B virus, Immune response, Inflammation.
(Please cite as Asadi P, Mohebbi SR, Hosseini SM, Zali MR. Evaluation of single nucleotide polymorphism in interleukin 22 (IL-22) gene and its association with chronic hepatitis B infection Gastroenterol Hepatol Bed Bench 2019;12(4):309-314).
World Health Organization. Global Alert and Response. Hepatitis B. Prevention and treatment. Available from: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index5.html.
You CR, Lee SW, Jang JW, Yoon SK. Update on hepatitis B virus infection. World J Gastroenterol 2014;20:13293-305.
Mohebbi SR, Cheraghipour K, Rostami Nejad M, Mohaghegh Shalmani H, Zali MR. Hepatitis C and hepatitis B virus infection: epidemiology and risk factors in a large cohort of pregnant women in Lorestan, West of Iran. Hepat Mon 2011;11:736-9.
Tahaei SM, Fatemi SR, Azimzadeh P, Mirsattari D, Sanati A, Sharifian A. Evaluation of antibody frequency against HBV, HCV and HTLV-1. Gastroenterol Hepatol Bed Bench 2012;5:161-5.
Noori S, Sarbazi MR, Safaee A, Farsar AR. Epidemiological features of hepatitis B and C infection in a high risk population: results of screening programs. Gastroenterol Hepatol Bed Bench 2013;6:136-40.
Romani S, Mohebbi SR, Boonstra A, Hosseini Razavi A, Sharifian A. Characterization of the "a" determinant region of the hepatitis B virus genome in Iranian patients at different clinical phases of chronic infection. Gastroenterol Hepatol Bed Bench 2018;11:131-7.
Mohebbi SR , Zali N, Noorinayer B, Derakhshan F, Chiani M, Rostami Nejad M, Antikchi MH, Sabahi F, Zali MR. Molecular epidemiology of hepatitis B virus in Iran. Clin Microbiol Infect 2008;14:858-66.
Liang TJ. Hepatitis B: the virus and disease. Hepatology 2009; S5:49.
Pellicoro A, Ramachandran P, Iredale JP, Fallowfield JA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol 2014;14:181-94.
Zhang Y, Cobleigh MA, Lian JQ, Huang CX, Booth CJ, Bai XF, et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology 2011;141:1897-906.
Thompson CL, Plummer SJ, Tucker TC, Casey G, Li L. Interleukin-22 genetic polymorphisms and risk of colon cancer. Cancer Causes Control 2010;21:1165-70.
Radaeva S, Sun R, Pan Hn, Hong F, Gao B. Interleukin 22 (IL‐22) plays a protective role in T cell‐mediated murine hepatitis: IL‐22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 2004;39:1332-42.
Wolk K, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004:241-54.
Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006;36(5):1309-23.
Endam LM, Bossé Y, Filali-Mouhim A, Cormier C, Boisvert P, Boulet L-P, et al. Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis. Otolaryngol Head Neck Surg 2009;140:741-7.
Azimzadeh P RS, Mirtalebi H, Fatemi SR, Kazemian S, Khanyaghma M, Mohebbi SR. Association of co-stimulatory human B-lymphocyte antigen B7-2 (CD86) gene polymorphism with colorectal cancer risk. Gastroenterol Hepatol Bed Bench 2013;6:86-91.
Najjar Sadeghi R SN, Vahedi M, Reza Mohebbi S, Reza Zali M. Association of intron and exon polymorphisms of p53 gene in Iranian patients with gastritis. Gastroenterol Hepatol Bed Bench 2013;6:S45-51.
Mansour AI, Abd Almonaem ER, Abd-Rabuh RM, Ahmed IAE. Association of interleukin (IL)-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms with susceptibility to pediatric autoimmune hepatitis type 1. Cytokine 2018;110:243-7.
Khanizadeh S, Mohebbi SR, Naghoosi H, Abrahim Tahaei M, Mousavi Nasab SD, Romani S, et al. Polymorphisms within the Promoter Region of the Gamma Interferon (IFN-γ) Receptor1 Gene are Associated with the Susceptibility to Chronic HBV Infection in an Iranian Population. Hepat Mon 2012;12:e7283.
Behelgardi A , Mohebbi SR, Azimzadeh P, Derakhshani S, Karimi K, Sharifian A, Zali MR. A Study on Genetic Association of Interleukin-16 Single Nucleotide Polymorphism (rs1131445) With Chronic Hepatitis B Virus Infection in Iranian Patients. Jundishapur J Microbiol 2015;14:e23411.
Karkhane M, Azimzadeh P, Avarandeh H, Kazemian S, Sharifian A, Hatami B, et al. Genetic association between a single nucleotide polymorphism in Interleukin-16 (rs4072111) and susceptibility to chronic HCV infection in an Iranian population. Gastroenterol Hepatol Bed Bench 2018;11:42-7.
Alabbas SY, Begun J, Florin TH, Oancea I. The role of IL-22 in the resolution of sterile and nonsterile inflammation. Clin Trans Immunol 2018;7:e1017.
Abe H, Kimura A, Tsuruta S, Fukaya T, Sakaguchi R, Morita R, et al. Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-gamma expression and inducing IL-22. Int Immunol 2014;26:129-37.
Zenewicz LA, Flavell RA. Recent advances in IL-22 biology. Int Immunol 2011;23:159-63.
Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 2008;29:947-57.
Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, et al. IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 2006;290:G827-38.
Weber GF, Gaertner FC, Erl W, Janssen K-P, Blechert B, Holzmann B, et al. IL-22-mediated tumor growth reduction correlates with inhibition of ERK1/2 and AKT phosphorylation and induction of cell cycle arrest in the G2-M phase. J Immunol 2006;177:8266-72.
Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, et al. Involvement of the IL-22/REG Iα axis in ulcerative colitis. Lab Invest 2010;90:496-505.
Zhang J, Zhao T, Xu C, Yu H. Four polymorphisms in the IL-22 gene and the risk of cancer: A meta-analysis. J Evid Based Med 2018;11:101-4.
Wang R, Zeng YL, Qin HM, Lu YL, Huang HT, Lei M, et al. Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population. Clin Exp Immunol 2018;193:143-51.
Marquet S, Conte I, Poudiougou B, Argiro L, Dessein H, Couturier C, et al. A functional IL22 polymorphism (rs2227473) is associated with predisposition to childhood cerebral malaria. Sci Rep 2017;7:41636.
Gao W, Fan YC, Zhang JY, Zheng MH. Emerging role of interleukin 22 in hepatitis B virus infection: a double-edged sword. J clin Trans Hepatol 2013;1:103-8.
Cobleigh MA, Robek MD. Protective and pathological properties of IL-22 in liver disease: implications for viral hepatitis. Am J Pathol 2013;182:21-8.
Sousa GM, Oliveira IS, Andrade LJ, Sousa-Atta ML, Parana R, Atta AM. Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection. Cytokine 2012;60:138-42.
Dambacher J, Beigel F, Zitzmann K, Heeg MH, Goke B, Diepolder HM, et al. The role of interleukin-22 in hepatitis C virus infection. Cytokine 2008;41:209-16.
Park O, Wang H, Weng H, Feigenbaum L, Li H, Yin S, et al. In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression. Hepatolology 2011;54:252-61.
Zhang JY, Zhang Z, Lin F, Zou ZS, Xu RN, Jin L, et al. Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology 2010;51:81-91.
Wang B, Zhao XP, Fan YC, Zhang JJ, Zhao J, Wang K. IL-17A but not IL-22 suppresses the replication of hepatitis B virus mediated by over-expression of MxA and OAS mRNA in the HepG2.2.15 cell line. Antiviral Res 2013;97:285-92.
Feng D, Kong X, Weng H, Park O, Wang H, Dooley S, et al. Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and patients with chronic hepatitis B virus infection. Gastroenterology 2012;143:188-98.