Aim: Our goal was to identify the putative association of rs4072111 variant in IL-16 gene and HCV susceptibility in an Iranian population.
Background: Interleukin 16 (IL-16), a multifunctional cytokine, plays a vital role in modulation of immune system.
Methods: In present case control and cross sectional study, IL-16 gene variant in 300 patients with hepatitis C (HCV) infection and 300 healthy individuals were analyzed. To evaluate this possible association, genomic DNA from venous blood was extracted and genotypes of IL-16 rs4072111 variant were determined by polymerase chain reaction- Fragments Length Polymorphism Technique (PCR-RFLP). Then, rs4072111 C/T genotypes frequency and allelic distribution were evaluated in each group.
Results: The results of genotyping showed 82% CC, 17.3% CT, 0.7% TT in the control group and 78% CC, 20% CT and 2% TT in the case group. The distribution of rs4072111 C allele was 90.7% in controls and 88% in case group respectively.
However, no correlation between IL-16 rs4072111 C/T variants and susceptibility to chronic HCV infection was found in the present study.
Conclusion: We concluded the rs4072111 C/T cannot be considered as a proper biomarker to identify susceptibility to chronic hepatitis C virus infection.
(Please cite as: Karkhane M, Mohebbi SR, Azimzadeh P, Avarandeh H, Kazemian SH, Sharifian A, 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(1):42-47).
Karkhane M, Mohebbi SR, Azimzadeh P, Niasar MS, Sarbazi MR, Sharifian A, et al. Lack of association between interleukin 28B gene polymorphisms (rs8099917G/T, rs12979860 C/T) and susceptibility to chronic hepatitis C virus infection, Tehran, Iran. Gastroenterology and hepatology from bed to bench. 2016;9(Suppl1):S29.
Radkowski M, Opoka-Kegler J, Cortes KC, Bukowska-Osko I, Perlejewski K, Pawelczyk A, et al. Evidence for immune activation in patients with residual hepatitis C virus RNA long after successful treatment with IFN and ribavirin. J Gen Virol. 2014;95:2004-9.
Liu Z, Zhang X, Yu Q, He JJ. Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochemical and biophysical research communications. 2014;455(3):218-22.
Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. The Journal of clinical investigation. 2009;119(7):1745.
Tester I, Smyk-Pearson S, Wang P, Wertheimer A, Yao E, Lewinsohn DM, et al. Immune evasion versus recovery after acute hepatitis C virus infection from a shared source. Journal of Experimental Medicine. 2005;201(11):1725-31.
Cox AL, Mosbruger T, Mao Q, Liu Z, Wang X-H, Yang H-C, et al. Cellular immune selection with hepatitis C virus persistence in humans. Journal of Experimental Medicine. 2005;201(11):1741-52.
Xu L-L, Song Z-C, Shang K, Zhao L-Q, Zhu Z-S. Non-association of IL-16 rs4778889 T/C polymorphism with cancer risk in Asians: a meta-analysis. 2014.
Skundric DS, Cruikshank WW, Drulovic J. Role of IL-16 in CD4+ T cell-mediated regulation of relapsing multiple sclerosis. J Neuroinflamm. 2015;12(1):78.
Mathy N, Scheuer W, Lanzendörfer M, Honold K, Ambrosius D, Norley S, et al. Interleukin‐16 stimulates the expression and production of pro‐inflammatory cytokines by human monocytes. Immunology. 2000;100(1):63-9.
Li S, Deng Y, Chen Z-P, Huang S, Liao X-C, Lin L-W, et al. Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population. Infection, Genetics and Evolution. 2011;11(8):2083-8.
Klimiuk PA, Goronzy JJ, Weyand CM. IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis. The Journal of Immunology. 1999;162(7):4293-9.
Musolino C, Allegra A, Innao V, Allegra AG, Pioggia G, Gangemi S. Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma. Mediators of inflammation. 2017;2017.
Behelgardi A, Hosseini SM, Mohebbi SR, Azimzadeh P, Derakhshani S, Karimi K, et al. A Study on Genetic Association of Interleukin-16 Single Nucleotide Polymorphism (rs1131445) With Chronic Hepatitis B Virus Infection in Iranian Patients. Jundishapur J Microb. 2015;8(11).
Akahane M, Watanabe M, Inoue N, Miyahara Y, Arakawa Y, Inoue Y, et al. Association of the polymorphisms of chemokine genes (IL8, RANTES, MIG, IP10, MCP1 and IL16) with the pathogenesis of autoimmune thyroid diseases. Autoimmunity. 2016;49(5):312-9.
Kashfi SMH, Farahbakhsh FB, Mojarad EN, Mashayekhi K, Azimzadeh P, Romani S, et al. Interleukin-16 polymorphisms as new promising biomarkers for risk of gastric cancer. Tumor Biol. 2016;37(2):2119-26.
Zhao YH, Tao L, Wang B, Nie P, Tang YM, Zhu M. Interleukin-16 Gene Polymorphisms rs4778889, rs4072111, rs11556218, and Cancer Risk in Asian Populations: A Meta-Analysis. Genet Test Mol Bioma. 2014;18(3):174-82.
Gao LB, Rao L, Wang YY, Liang WB, Li C, Xue H, et al. The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer. Carcinogenesis. 2009;30(2):295-9.
Liu C, Mills J, Dixon K, Vennarini J, Cunningham M, Del Vecchio A, et al. IL-16 signaling specifically induces STAT6 activation through CD4. Cytokine. 2007;38(3):145-50.
Amiel C, Darcissac E, Truong M-J, Dewulf J, Loyens M, Mouton Y, et al. Interleukin-16 (IL-16) inhibits human immunodeficiency virus replication in cells from infected subjects, and serum IL-16 levels drop with disease progression. The Journal of infectious diseases. 1999;179(1):83-91.
Bengsch B, Thimme R, Blum HE. Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection. Viruses-Basel. 2009;1(2):104-25.
Romani S, Hosseini SM, Mohebbi SR, Kazemian S, Derakhshani S, Khanyaghma M, et al. Interleukin-16 gene polymorphisms are considerable host genetic factors for patients’ susceptibility to chronic hepatitis B infection. Hepatitis research and treatment. 2014;2014.
Alhazmi A, Alwakeel H. Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi patients.