Interferon gamma signaling pathway is an important trigger for activating antiviral immune responses and production of wide variety of molecules with anti-microbial profiles including type 1 cytokines. Any defect or variation in IFNG signaling pathway may result in susceptibility or progression to diverse diseases such as inflammatory and virus associated disorders. Rs1327474 A/G also known as -611 A/G is an important variation which is located in promoter region of IFNGR1 and may have potent risk for HCV susceptibility. In present survey, we attempted to inquire the plausible linkage of rs1327474 A/G and HCV chronic infection or the clearance of the virus. For this purpose, 154 HCV patients and 200 normal controls were enrolled in the study, and genomic DNA was isolated from PBMCS and IFNGR1 -611 polymorphism was genotyped by polymerase chain reaction- Fragments Length Polymorphism (PCR-RFLP) method. While, AA, AG and GG genotype frequency included 37.8%, 53.7%, 8.5% in healthy controls, 41.6%, 46.1%, 12.3% were found in chronic HCV patients. Interestingly, allelic percentage was similar in both separated groups within 64.7%, 35.3% and 65.3%, 34.7% were obtained for T and G allele in control and case group respectively. Despite of our exception for the possible role of this variation in an important promoter region of IFGR1 gene, rs1327474 A/G was not associateed with HCV chronic infection among an Iranian studied group. Comprehensively, -611A/G cannot consider as a risk biomarker for susceptibility to chronic HCV disease.
Kao J-H. Hepatitis C virus infection in Taiwan: Past, present, and future. J. Formos. Med. Assoc. 2016; 115(2):65-6.
Umer M, Iqbal M. Hepatitis C virus prevalence and genotype distribution in Pakistan: Comprehensive review of recent data. World J. Gastroenterol. 2016; 22(4):1684.
Alric L, Fort M, Izopet J, Vinel JP, Bureau C, Sandre K, et al. Study of host‐and virus‐related factors associated with spontaneous hepatitis C virus clearance. HLA 2000; 56(2):154-8.
Karkhane M, Mohebbi SR, Azimzadeh P, Avarandeh H, Kazemian S, 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. Gastroenterology and Hepatology from bed to bench 2018.
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.
Karkhane M, Mohebbi SR, Azimzadeh P, Derakhshani S, Sharifian A, Golmohammadi A, et al. Evaluation of the association between interleukin28B gene polymorphisms and chronic hepatitis C virus infection. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch 2016; 26(1):30-5.
Korachi M, Ceran N, Adaleti R, Nigdelioglu A, Sökmen M. An association study of functional polymorphic genes IRF-1, IFNGR-1, and IFN-γ with disease progression, aspartate aminotransferase, alanine aminotransferase, and viral load in chronic hepatitis B and C. Int. J. Infect. Dis. 2013; 17(1):e44-e9.
Schoenborn JR, Wilson CB. Regulation of interferon‐γ during innate and adaptive immune responses. Adv. Immunol. 2007; 96:41-101.
Arellano G, Ottum PA, Reyes LI, Burgos PI, Naves R. Stage-specific role of interferon-gamma in experimental autoimmune encephalomyelitis and multiple sclerosis. Front. Immunol. 2015; 6:492.
Rus V, Via CS. 12 Cytokines in Systemic Lupus Erythematosus. Systemic Lupus Erythematosus E-Book: A Companion to Rheumatology 2007:108.
Dai C-Y, Chuang W-L, Hsieh M-Y, Lee L-P, Hou N-J, Chen S-C, et al. Polymorphism of interferon–gamma gene at position+ 874 and clinical characteristics of chronic hepatitis C. Translational Research 2006; 148(3):128-33.
Bulat‐Kardum L, Etokebe G, Knezevic J, Balen S, Matakovic‐Mileusnic N, Zaputovic L, et al. Interferon‐γ Receptor‐1 Gene Promoter Polymorphisms (G‐611A; T‐56C) and Susceptibility to Tuberculosis. Scand. J. Immunol. 2006; 63(2):142-50.
Khanizadeh S, Ravanshad M, Mohebbi SR, Naghoosi H, Tahaei MA, Nasab SDM, 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. Hepatitis monthly 2012; 12(11).
Deckert-Schlüter M, Rang A, Weiner D, Huang S, Wiestler OD, Hof H, et al. Interferon-gamma receptor-deficiency renders mice highly susceptible to toxoplasmosis by decreased macrophage activation. Laboratory investigation; a journal of technical methods and pathology 1996; 75(6):827-41.
Dorman SE, Picard C, Lammas D, Heyne K, van Dissel JT, Baretto R, et al. Clinical features of dominant and recessive interferon γ receptor 1 deficiencies. The Lancet 2004; 364(9451):2113-21.
Auerbuch V, Brockstedt DG, Meyer-Morse N, O'Riordan M, Portnoy DA. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J. Exp. Med. 2004; 200(4):527-33.
Torres O, Palomino-Morales R, Vazquez-Rodriguez T, Castañeda S, Morado I, Miranda-Filloy J, et al. Lack of association between IFNGR1 gene polymorphisms and biopsy-proven giant cell arteritis. Clin. Exp. Rheumatol. 2010; 28(1):S31.
Sambrook J, Russell DW. Molecular cloning: a laboratory manual. 2001. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 2001.
Walker AJ, Peacock CJ, Pedergnana V, Irving WL. Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: A systematic review. J. Viral Hepat. 2018.
Matsuura K, Tanaka Y. Host genetic variants influencing the clinical course of hepatitis C virus infection. J. Med. Virol. 2016; 88(2):185-95.
Griffiths SJ, Dunnigan CM, Russell CD, Haas JG. The role of interferon-λ locus polymorphisms in hepatitis C and other infectious diseases. J. Innate Immun. 2015; 7(3):231-42.
Berger K, Scherer J, Ranga M, Sha N, Stern J, Quinson A-M, et al. Baseline polymorphisms and emergence of drug resistance in the NS3/4A protease of hepatitis C virus genotype 1 following treatment with faldaprevir and pegylated interferon alpha 2a/ribavirin in phase 2 and phase 3 studies. Antimicrob. Agents Chemother. 2015; 59(10):6017-25.
de Vosse E, Dissel JT. IFN‐γR1 defects: Mutation update and description of the IFNGR1 variation database. Hum. Mutat. 2017.
Izad M, Vodjgani M, NIKNAM M, AMIRZARGAR AA, LOTFI J, FATHI D. Interferon-gamma gene polymorphism in Iranian patients with multiple sclerosis. 2004.
Mirsaeidi S, Houshmand M, Tabarsi P, Banoei M, Zargari L, Amiri M, et al. Lack of association between interferon‐gamma receptor‐1 polymorphism and pulmonary TB in Iranian population sample. J. Infect. 2006; 52(5):374-7.
Naderi M, Hashemi M, Rezaei M, Safdari A. Association of genetic polymorphisms of IFNGR1 with the risk of pulmonary tuberculosis in Zahedan, Southeast Iran. Tuberculosis research and treatment 2015; 2015.
He S, Wang B, Zhu X, Chen Z, Chen J, Hua D, et al. Association of IFNGR1 and IFNG genetic polymorphisms with the risk for pulmonary tuberculosis in the Chinese Tibetan population. Oncotarget 2017; 8(58):98417.
Velayati AA, Farnia P, Khalizadeh S, Farahbod AM, Hasanzadh M, Sheikolslam MF. Interferon-gamma receptor-1 gene promoter polymorphisms and susceptibility to leprosy in children of a single family. The American journal of tropical medicine and hygiene 2011; 84(4):627-9.
Wang L, Wang Y, Song Z, Chu J, Qu X. Deficiency of interferon-gamma or its receptor promotes colorectal cancer development. J. Interferon Cytokine Res. 2015; 35(4):273-80.
Heidari Z, Mahmoudzadeh-Sagheb H, Hashemi M, Ansarimoghaddam S, Moudi B, Sheibak N. Association between IFN-γ. International journal of dentistry 2015; 2015.