Genetic Susceptibility in Family Members of Egyptian Hepatitis C Virus Infected Patients: Role of Interleukin-12 B Gene Polymorphism

Author(s): Nadia Elwan, Nadia Elwan, Fathia Assal, Fathia Assal, Asem Elfert, Asem Elfert, Lobna AboAli, Lobna AboAli, Shaimaa Soliman, Shaimaa Soliman, Samah Soliman, Samah Soliman, Walaa Elkhalawany, Walaa Elkhalawany, Rehab Badawy, Rehab Badawy, Laila Effat, Laila Effat, Khalda Sayed, Khalda Sayed, Safinaz Shalaby, Safinaz Shalaby, Marwa Shehab, Marwa Shehab, Mohamed Abdel-Hamid, Mohamed Abdel-Hamid, Sherief Abd-Elsalam*, Sherief Abd-Elsalam*.

Journal Name: Infectious Disorders - Drug Targets

Volume 19 , Issue 1 , 2019

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Graphical Abstract:


Abstract:

Aim: The research was conducted to study 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes in families of Hepatitis C virus (HCV) infected patients in Egypt.

Methods: Three hundreds HCV patients, 860 family members and 100 healthy subjects were studied. All family members were screened for HCV antibodies by enzyme-linked immunosorbent assay (ELISA). Positive cases were examined using Real-Time polymerase chain reaction (PCR) to confirm the presence of HCV ribonucleic acid (RNA) and detect the viral load. Molecular study of IL-12B gene was carried out on all patients, family members and controls using PCR and restriction enzyme analysis.

Results: HCV infection was confirmed in 10.6% of family members. The distribution of IL-12B gene polymorphism in patients was 2.3%, 45.7% and 52% for C/C, A/C and A/A genotypes respectively, in infected family members was 3.3%, 41.7%, 55%, in noninfected family members was 4.5%, 43.5% and 52% for C/C, A/C and A/A genotypes respectively and in control was 5%, 36% and 59% for C/C, A/C and A/A genotypes respectively. The frequency of the C/C, A/C and A/A genotype was not significantly different between the studied groups.

Conclusion: IL-12B gene polymorphism has no role in intrafamilial susceptibility of HCV transmission. The distribution of the functional 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes was not significantly different among the studied groups.

Keywords: Gene, HCV, IL12B, intrafamilial transmission, polymorphism, genepolymorphism.

[1]
Lavanchy, D. Evolving epidemiology of hepatitis C virus. Clin. Microbiol. Infect., 2011, 17(2), 107-115.
[2]
Elwan, N.; Elfert, A.; Abd-Elsalam, S. Study of Hepatic Steatosis Index in Patients with Chronic HCV Infection. Int. J. Curr. Microbiol. Appl. Sci., 2016, 5(5), 266-274.
[3]
Guerra, J.; Garenne, M.; Mohamed, M.K.; Fontanet, A. HCV burden of infection in Egypt: results from a nationwide survey. J. Viral Hepat., 2012, 19(8), 560-567.
[4]
Abd-Elsalam, S.; Sharaf-Eldin, M.; Soliman, S.; Elfert, A.; Badawi, R.; Ahmad, Y.K. Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice. Arch. Virol., 2018, 163(1), 51-56.
[5]
Ahmed, O.A.; Kaisar, H.H.; Hawash, N.; Samir, H.; Shabana, S.S.T.; Hassan A Fouad, M.; Rizk, F.; Abd-Elsalam, S. Efficacy of Sofosbuvir Plus Ribavirin with or Without Peginterferon- Alfa in Treatment of a Cohort of Egyptian Patients with Hepatitis C Virus Infection. Infect. Disord. Drug Targets, 2017, 17(2), 95-100.
[6]
Rodger, A.J.; Roberts, S.; Lanigan, A.; Bowden, S.; Brown, T.; Crofts, N. Assessment of long-term outcomes of community-acquired hepatitis C infection in a cohort with sera stored from 1971 to 1975. Hepatology, 2000, 32(3), 582-587.
[7]
Zaki, M.E.; Amr, K.S.; Abdel-Hamid, M. APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism. Cholesterol, 2013, 2013, 289481.
[8]
Youssef, S.S.; Abd El Aal, A.M.; Nasr, A.S.; el Zanaty, T.; Seif, S.M.; Seif, S. Interleukin-12B gene polymorphism frequencies in Egyptians and sex-related susceptibility to hepatitis C infection. J. Interferon Cytokine Res., 2013, 33(8), 415-419.
[9]
Shepard, C.W.; Finelli, L.; Alter, M.J. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis., 2005, 5(9), 558-567.
[10]
Magder, L.S.; Fix, A.D.; Mikhail, N.N.; Mohamed, M.K.; Abdel-Hamid, M.; Abdel-Aziz, F.; Medhat, A.; Strickland, G.T. Estimation of the risk of transmission of hepatitis C between spouses in Egypt based on seroprevalence data. Int. J. Epidemiol., 2005, 34(1), 160-165.
[11]
Indolfi, G.; Bartolini, E.; Azzari, C.; Becciolini, L.; Moriondo, M.; de Martino, M.; Resti, M. Intrafamilial transmission of hepatitis C virus: infection of the father predicts the risk of perinatal transmission. J. Med. Virol., 2008, 80(11), 1907-1911.
[12]
Minola, E.; Baldo, V.; Baldovin, T.; Trivello, R.; Floreani, A. Intrafamilial transmission of hepatitis C virus infection. Eur. J. Epidemiol., 2006, 21(4), 293-297.
[13]
Plancoulaine, S.; Mohamed, M.K.; Arafa, N.; Bakr, I.; Rekacewicz, C.; Trégouët, D.A.; Obach, D.; El Daly, M.; Thiers, V.; Féray, C.; Abdel-Hamid, M.; Abel, L.; Fontanet, A. Dissection of familial correlations in hepatitis C virus (HCV) seroprevalence suggests intrafamilial viral transmission and genetic predisposition to infection. Gut, 2008, 57(9), 1268-1274.
[14]
El-Bendary, M.; Esmat, G. Epidemiological Aspects of Intrafamilial Spread of HCV Infection in Egyptian Population: A Pilot Study. Open Journal of Gastroenterology, 2014, 4, 228-236.
[15]
Elwan, N.; Amr, K.; Elyamany, S.; Elkhalawany, W.; Soliman, S.; Ziada, M.; Abd-Elsalam, S. Association of IL-12 B Gene Polymorphism with Staging of Liver Disease in Chronic HCV Patients. Infect. Disord. Drug Targets, 2017, 17, 122-128.
[16]
Wan, L.; Kung, Y.J.; Lin, Y.J.; Liao, C.C.; Sheu, J.J.; Tsai, Y.; Lai, H.C.; Peng, C.Y.; Tsai, F.J. Th1 and Th2 cytokines are elevated in HCV-infected SVR(-) patients treated with interferon-alpha. Biochem. Biophys. Res. Commun., 2009, 379(4), 855-860.
[17]
Del Vecchio, M.; Bajetta, E.; Canova, S.; Lotze, M.T.; Wesa, A.; Parmiani, G.; Anichini, A. Interleukin-12: biological properties and clinical application. Clin. Cancer Res., 2007, 13(16), 4677-4685.
[18]
Elwan, N.; Assal, F.; El-fert, A. P6A: Role of IL-12B and IL-28B gene polymorphisms in families of HCV infected patients in the Nile Delta of Egypt. J. Viral Hepat., 2013, 20(s3), 41-42.
[19]
Trinchieri, G.; Pflanz, S.; Kastelein, R.A. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity, 2003, 19(5), 641-644.
[20]
El-Bassat. H Interleukin 23 P 19 Gene Expressions in Patients with Ulcerative Colitis and its Relation to Disease Severity. J. Dis. Markers, 2014, 1(1), 1004.
[21]
Prezzi, C.; Casciaro, M.A.; Francavilla, V.; Schiaffella, E.; Finocchi, L.; Chircu, L.V.; Bruno, G.; Sette, A.; Abrignani, S.; Barnaba, V. Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection. Eur. J. Immunol., 2001, 31(3), 894-906.
[22]
Peters, M. Actions of cytokines on the immune response and viral interactions: an overview. Hepatology, 1996, 23(4), 909-916.
[23]
Biron, C.A. Cytokines in the generation of immune responses to, and resolution of, virus infection. Curr. Opin. Immunol., 1994, 6(4), 530-538.
[24]
Huang, D.; Cancilla, M.R.; Morahan, G. Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun., 2000, 1(8), 515-520.
[25]
Seegers, D.; Zwiers, A.; Strober, W.; Peña, A.S.; Bouma, G. A TaqI polymorphism in the 3'UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun., 2002, 3(7), 419-423.
[26]
Mueller, T.; Mas-Marques, A.; Sarrazin, C. Correspondence "Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection". J. Hepatol., 2004, 41(4), 652-658.
[27]
Hegazy, D.; Thurairajah, P.; Metzner, M.; Houldsworth, A.; Shaw, S.; Kaminski, E.; Demaine, A.G.; Cramp, M.E. Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection. Clin. Exp. Immunol., 2008, 152(3), 538-541.
[28]
Dondeti, M.F.; El-Maadawy, E.A.; Talaat, R.M. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms. World J. Gastroenterol., 2016, 22(30), 6800-6816.
[29]
Houldsworth, A.; Metzner, M.; Hodgkinson, A.; Shaw, S.; Kaminski, E.; Demaine, A.G.; Cramp, M.E. Haplotype analysis finds linkage disequilibrium in the IL-12 gene in patients with HCV. J. Med. Virol., 2015, 87(7), 1207-1217.
[30]
Zhu, B.; Wang, C.; Zhang, X.; He, J.; Wu, J.; Yu, R.; Zhao, W. Relationships between interleukin-12B and interleukin-10 gene polymorphisms and hepatitis C in Chinese Han hemodialysis patients. Ren. Fail., 2015, 37(3), 505-510.
[31]
Suneetha, P.V.; Goyal, A.; Hissar, S.S.; Sarin, S.K. Studies on TAQ1 polymorphism in the 3'untranslated region of IL-12P40 gene in HCV patients infected predominantly with genotype 3. J. Med. Virol., 2006, 78(8), 1055-1060.


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Article Details

VOLUME: 19
ISSUE: 1
Year: 2019
Page: [81 - 87]
Pages: 7
DOI: 10.2174/1871526518666171227210541
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