Background: Single nucleotide polymorphisms and variant expression of some interferon (IFN) genes in individuals with chronic hepatitis B virus (HBV) infection might be related to higher viral load and disease complications. Thereby, whole blood samples of 208 patients (94 chronic HBV-infected patients and 114 HBV immune subjects) were analyzed to investigate the association between IFNG (-5A→G), IFNA1 (-2C→T) and IFNAR1 (-97T→C) genes with their expression levels and HBV viral load. Methods: Genotyping was performed by high-resolution melting analysis with quantitative PCR (qPCR). Viral load quantification and gene expression were also carried out using qPCR. Results: Chronic HBV-infected subjects with IFNA1 CT genotype and T allele were more likely to develop protection against HBV when compared to immune subjects with wild-type genotype (IFNA1 CT/CC: OR = 0.45, p = 0.01, and T/C allele: OR = 0.55; p < 0.01). In patients with IFNAR1 wild-type TT genotype, the expression levels of this receptor may explain the lower viral load (r2 = 0.40; p = 0.04) and protection against chronic infection. Conclusions: These findings suggest that the polymorphic variant of IFNA1 (-2) gene is associated with chronic HBV infection, and high expression levels of the IFNAR1 gene and low levels of IFNA1 might contribute to the pathogenesis of chronic infection in these subjects.

1.
Lavanchy D: Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97-107.
2.
Fattovich G: Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47-58.
3.
Ganem D, Prince AM: Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 2004;350:1118-1129.
4.
Lok ASF, McMahon BJ: Chronic hepatitis B. Hepatology 2007;45:507-539.
5.
Hou J, Liu Z, Gu F: Epidemiology and prevention of hepatitis B virus infection. Int J Med Sci 2005;2:50-57.
6.
Pereira L, Martelli C, Merchán-Hamann E, Montarroyos U, Braga M, de Lima M, et al: Population-based multicentric survey of hepatitis B infection and risk factor differences among three regions in Brazil. Am J Trop Med Hyg 2009;81:240-247.
7.
Yim HJ, Lok AS-F: Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology 2006;43:S173-S181.
8.
Wang S, Huang D, Sun S, Ma W, Zhen Q: Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa. Virol J 2011;8:28.
9.
Conde SRS, Feitosa RNM, Freitas FB, Hermes RB, Demachki S, Araújo MTF, et al: Association of cytokine gene polymorphisms and serum concentrations with the outcome of chronic hepatitis B. Cytokine 2013;61:940-944.
10.
Komatsu H, Murakami J, Inui A, Tsunoda T, Sogo T, Fujisawa T: Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children. BMC Res Notes 2014;7:1-9.
11.
Almajhdi FN, Al-ahdal M, Abdo AA, Sanai FM, Al-anazi M: Single nucleotide polymorphisms in CXCR1 gene and its association with hepatitis B infected patients in Saudi Arabia. Ann Hepatol 2013;12:220-227.
12.
Chang S-W, Fann CS-J, Su W-H, Wang YC, Weng CC, Yu C-J, et al: A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese. PLoS One 2014;9:1-10.
13.
He X-X, Chang Y, Jiang H-J, Tang F, Meng F-Y, Xie Q-H, et al: Persistent effect of IFNAR-1 genetic polymorphism on the long-term pathogenesis of chronic HBV infection. Viral Immunol 2010;23:251-257.
14.
Gao Q-J, Liu D-W, Zhang S-Y, Li-Min W, Wu L-H, Wang S-Y, et al: Polymorphisms of some cytokines and chronic hepatitis B and C virus infection. World J Gastroenterol 2009;15:5610-5619.
15.
Kim SS, Cheong JY, Lee D, Lee SK, Kim M-H, Kwack K, et al: Interleukin-1ß and interleukin-1 receptor accessory protein gene polymorphisms are associated with persistent hepatitis B virus infection. Hepatogastroenterology 2012;59:190-197.
16.
Kimkong I, Tangkijvanich P, Hirankarn N: Association of interferon-alpha gene polymorphisms with chronic hepatitis B virus infection. Int J Immunogenet 2013;40:476-481.
17.
Zhou J, Smith DK, Lu L, Poon VKM, Ng F, Chen D-Q, et al: A non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infection. J Viral Hepat 2009;16:45-52.
18.
Song LH, Toan NL, Xuan NT, Uhlemann A-C, Boldt ABW, Duy DN, et al: A promoter polymorphism in the interferon alpha-2 gene is associated with the clinical presentation of hepatitis B. Mutat Res 2006;601:137-143.
19.
Diop G, Hirtzig T, Do H, Coulonges C, Vasilescu A, Labib T, et al: Exhaustive genotyping of the interferon alpha receptor 1 (IFNAR1) gene and association of an IFNAR1 protein variant with AIDS progression or susceptibility to HIV-1 infection in a French AIDS cohort. Biomed Pharmacother 2006;60:569-577.
20.
Kreil S, Waghorn K, Ernst T, Chase A, White H, Hehlmann R, et al: A polymorphism associated with STAT3 expression and response of chronic myeloid leukemia to interferon α. Haematologica 2010;95:148-152.
21.
Sambrook J, Russel DW: Molecular cloning: a laboratory manual; in: Protocol 1 - Isolation of High-Molecular-Weight DNA from Mammalian Cells Using Proteinase K and Phenol, ed 3. New York, Cold Spring Harbor Laboratory Press, 2001, pp 6.4-6.11.
22.
Jiang E, Li F, Jing C, Li P, Cui H, Wang B, et al: High-resolution melting analysis as a developed method for genotyping the PD susceptibility loci in LRRK2 gene. J Clin Lab Anal 2015;29:299-304.
23.
Vali Z, Raz A, Bokharaei H, Nabavi M: Development of a high-resolution melting analysis method based on SYBR Green-I for rs7216389 locus genotyping in asthmatic child patients. Avicenna J Med Biotechnol 2014;6:72-80.
24.
European Association for the Study of the Liver: EASL Clinical Practice Guidelines: management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185.
25.
Leong D, Gupta A, Bai H, Wan G, Yoong L, Too H, et al: Absolute quantification of gene expression in biomaterials research using real-time PCR. Biomaterials 2007;28:203-210.
26.
Manly KF: Reliability of statistical associations between genes and disease. Immunogenetics 2005;57:549-558.
27.
Ait-Goughoulte M, Lucifora J, Zoulim F, Durantel D: Innate antiviral immune responses to hepatitis B virus. Viruses 2010;2:1394-1410.
28.
Pan CQ, Zhang JX: Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci 2005;2:36-40.
29.
Kondo Y, Kobayashi K, Ueno Y, Shiina M, Niitsuma H, Kanno N, et al: Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B. World J Gastroenterol 2006;12:4310-4317.
30.
Uno K, Suginoshita Y, Kakimi K, Moriyasu F, Hirosaki M, Shirakawa T, et al: Impairment of IFN-alpha production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma. World J Gastroenterol 2005;11:7330-7334.
31.
Wu D, Liu F, Li J, Liu C, Liu L, Tang H, et al: Intrahepatic IFN-alpha expression in liver specimens from HBV-infected patients with different outcomes. Eur Rev Med Pharmacol Sci 2013;17:2474-2480.
32.
Li Y, Wang J-J, Gao S, Liu Q, Bai J, Zhao X-Q, et al: Decreased peripheral natural killer cells activity in the immune activated stage of chronic hepatitis B. PLoS One 2014;9:1-8.
33.
Bream J, Ping A, Zhang X, Winkler C, Young H: A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription. Genes Immun 2002;3:165-169.
34.
Toyonaga T, Hino O, Sugai S, Wakasugi S, Abe K, Schichiri M, et al: Chronic active hepatitis in transgenic mice expressing interferon-γ in the liver. Proc Natl Acad Sci USA 1994;91:614-618.
35.
Young H, Klinman D, Reynolds D, Grzegorzewski K, Nii A, Ward J, et al: Bone marrow and thymus expression of interferon-gamma results in severe B-cell lineage reduction, T-cell lineage alterations, and hematopoietic progenitor deficiencies. Blood 1997;89:583-595.
36.
Ribeiro CSS, Visentainer JEL, Moliterno RA: Association of cytokine genetic polymorphism with hepatitis B infection evolution in adult patients. Mem Inst Oswaldo Cruz 2007;102:435-440.
37.
Corrêa Bde M, Lopes EP, Albuquerque Mde F, Dourado L: Association between HLA-DRB1* polymorphisms and hepatitis B infection in a Brazilian population. Rev Assoc Med Bras 2012;58:537-542.
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