Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations

Gülay Börekçi; İrem Bekalp; Özlem Kandemir; Ayşegül Çetinkaya; Gülhan Orekici Temel; Nurcan Aras

Research Article

Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations

Year 2020, Volume: 5 Issue: 4, 123 - 132, 31.12.2020

Gülay Börekçi İrem Bekalp Özlem Kandemir Ayşegül Çetinkaya Gülhan Orekici Temel Nurcan Aras

Abstract

Background/Aims: This study aimed to determine the relationship between TNF-α (-1031 T/C), IL-12A (3'UTR G/A), IL-12B (3'UTR A/C) and IFN-γ (+874 A/T) gene polymorphisms and chronic hepatitis B infections.
Materials and Methods: 100 patients with chronic hepatitis B and 100 healthy subjects were included in this study. Approximately 2 ml of peripheral blood from patient and control groups were taken into tubes with EDTA and the genomic DNA was isolated by using the DNA isolation kit. Single nucleotide polymorphisms (SNPs) in TNF-α (-1031 T/C), IL-12A (3'UTR G/A), IL-12B (3'UTR A/C) and IFN-γ (+874 A/T) genes were investigated by using RT-PCR method.
Results: It was determined that there was no statistically significant difference in terms of the allele and genotype frequencies of TNF-α (T/C) and IFN-γ (A/T) between chronic hepatitis B patients and the control group (p>0.05). However, there was a statistically significant difference between the patient and control groups for IL-12A (G/A) and IL-12B (A/C) in terms of genotype and allele distributions. The frequencies of IL-12A GG and GA genotypes (OR: 0.814, 95% 0.369-1.795, p=0.001) in patient group, and AA genotype in control group (OR: 2.608 95% 1.189-5.720, p=0.001) were high. Futhermore, it was found that the frequencies of IL-12A G allele in patient group and A allele in control group (OR: 1.981, 95%1.115-2.462, p=0.001) were high. In terms of IL-12B genotype and allele distributions, the frequencies of AC genotype (OR: 0.131, 95% 0.049-0.350, p=0.001) and A allele was higher in the patient group than the control group, whereas C allele in the control group was high. (OR:1.657, 1.115-2.462, p=0.012).
Conclusion: Our results showed that TNF-α (-1031 T/C), and IFN-γ (+874 A/T) polymorphism is not effective in chronic HBV infections. However, IL-12A (3'UTR G/A) and IL-12B (3'UTR A/C) polymorphisms may influence the chronicity of hepatitis B.

Keywords

Chronic hepatitis B, polymorphism, TNF-α, IL-12, IFN-γ, SNP

Supporting Institution

Mersin Üniversity Scientific Research Projects Unit

Project Number

Project no: 2015-AP4-1203

References

1. Previsani N, Lavanchy D (2002) Hepatitis B. Department of Communicable Diseases Surveillance and Response, World Health Organisation, Geneva.
2. WHO (2017) Global Hepatitis Report. https://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455eng.pdf?sequence=1. Accessed 10 April 2020
3. Romagnani S (1999) Th1/Th2 cells. Inflamm Bowel Dis 5(4):285-94.
4. Başkan EB (2013) [T hücre immunitesi]. Turkderm 47(SUPPL.1):18-23.
5. Zhang G, Li Z, Han Q, et al (2011) Altered TNF-α and IFN-γ levels associated with PD1 but not TNFA polymorphisms in patients with chronic HBV infection. Infect Genet Evol 11(7):1624-30.
6. Ferreira Sda C, Chachá SG, Souza FF, et al (2015) IL-18, TNF, and IFNγ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury. J Med Virol 87(10):1689-96.
7. Kim YJ, Lee HS, Yoon JH, et al (2003) Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. Hum Mol Genet 12(19):2541-6.
8. Lu LP, Li XW, Liu Y, et al (2004) Association of -238G/A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population. World J Gastroenterol 10(12):1810-4.
9. Talaat RM, Abdelkhalek MS, El-Maadawy EA, Abdel-Mageed WS, El-Shenawy SZ, Osman MA (2017) Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B virus infection in Egyptians. Hum Immunol 78(11-12):739-46.
10. Fletcher GJ, Samuel P, Christdas J, et al (2011) Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population. Genes Immun 12(7):552-8.
11. Sghaier I, Zidi S, Mouelhi L, et al (2015) The relationship between TNF alpha gene polymorphisms (-238/308), TNF RII VNTR (p75) and outcomes of hepatitis B virus infection in Tunisian population. Gene 568(2):140-5.
12. Xia Q, Zhou L, Liu D, Chen Z, Chen F (2011) Relationship between TNF-<alpha> gene promoter polymorphisms and outcomes of hepatitis B virus infections: a meta-analysis. PLoS One 10;6(5).
13. Jin YJ, Lee D, Chung YH, et al (2015) Tumor necrosis factor-alpha gene polymorphism associated with development of hepatitis B virus-associated hepatocellular carcinoma. J Clin Gastroenterol 49(8):e76-81.
14. Tsuchiya N, Tokushige K, Yamaguchi N et al (2004) Influence of TNF gene polymorphism in patients with acute and fulminant hepatitis. J Gastroenterol 39(9):859-66.
15. Liu W, Wei H, Liang S, Zhang J, Sun R, Tian Z (2004) A balanced expression of two chains of heterodimer protein, the human interleukin-12, improves high-level expression of the protein in CHO cells. Biochem Biophys Res Commun 313(2):287-93.
16. Zheng Y, Wang M, Tian T, et al (2017) Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta-analysis. Oncotarget 8(18):29795-807.
17. Yuzhalin AE, Kutikhin AG (2012) Interleukin-12: clinical usage and molecular markers of cancer susceptibility. Growth Factors 30(3):176-91.
18. Liu L, Xu Y, Liu Z, et al (2011) IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 128(7):1692-6.
19. Grzegorzewska AE, Wobszal PM, Sowińska A, Mostowska A, Jagodziński PP (2013) Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection. Mol Biol Rep 40(12):6899-911.
20. Tau G, Rothman P (1999) Biologic functions of the IFN-gamma receptors. Allergy 54(12):1233-51.
21. Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-γ. Annu Rev Immunol 15(1):749-95.
22. Wei Y, Tian Q, Li L, Zhang D (2016) Association between IFN-γ genetic polymorphisms and susceptibility to hepatitis B virus infection: A meta-analysis. Ann Hum Biol 43(6):527-36.
23. Naghizadeh MS, Naseri M, Fereidouni M, et al (2018) Single nucleotide polymorphism of the interferon-γ gene (IFN-γ +874 T/A) and the prognosis of hepatitis B infection. J Med Microbiol Infect Dis 6(2-3):43-47.
24. Sun Y, Lu Y, Xie L, Deng Y, Li S, Qin X (2015) Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population. Cancer Cell Int 31;15:35.
25. Ji L, Zeng X, Li L, Qiu X, Chen S, Yu H (2011) Interaction between the single-nucleotide polymorphism of DNA repair gene hOGG1 and HBV infection and its susceptibility to hepatocellular carcinoma. Wei Sheng Yan Jiu 40(6):705-8.
26. Liu Y, Guo XH, Du T, et al (2005) Association of TNFA polymorphisms with the outcomes of HBV infection. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;22(4):406-10.
27. Park JS, Cheong JY, Kang JK, et al (2007) Association of interleukin-12 gene polymorphism with persistence of hepatitis B virus infection and hepatocellular carcinoma. Korean J Gastroenterol 50(5): 313-8.
28. Tan A, Gao Y, Yao Z, et al (2016) Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population. Tumour Biology 37(5):6343-8.
29. Chen X, Han S, Wang S, et al (2009) Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res. 1;15(1):400-5.
30. Ghasemian N, Shahbazi M (2016) Interferon gamma gene polymorphism (+874 T>A) and chronic hepatitis B in the Population of Gorgan, North Eastern Iran. Jundishapur J Microbiol 9(8):e33639.
31. Al Kadi M, Monem F (2017) Polymorphism of IFN-γ (+874 T/A) in Syrian patients with chronic hepatitis B. Gastroenterol Hepatol Bed Bench 10(1):34-38.
32. Ji L, Zeng X, Li L, Qiu X, Chen S, Yu H (2011) Interaction between the single-nucleotide polymorphism of DNA repair gene hOGG1 and HBV infection and its susceptibility to hepatocellular carcinoma. Wei Sheng Yan Jiu 40(6):705-8.
33. Gao QJ, Xie JX, Wang LM, Zhou Q, Zhang SY (2017) Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study. BMJ Open 23;7(8):e013279.

Year 2020, Volume: 5 Issue: 4, 123 - 132, 31.12.2020

Gülay Börekçi İrem Bekalp Özlem Kandemir Ayşegül Çetinkaya Gülhan Orekici Temel Nurcan Aras

Abstract

Project Number

Project no: 2015-AP4-1203

References

1. Previsani N, Lavanchy D (2002) Hepatitis B. Department of Communicable Diseases Surveillance and Response, World Health Organisation, Geneva.
2. WHO (2017) Global Hepatitis Report. https://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455eng.pdf?sequence=1. Accessed 10 April 2020
3. Romagnani S (1999) Th1/Th2 cells. Inflamm Bowel Dis 5(4):285-94.
4. Başkan EB (2013) [T hücre immunitesi]. Turkderm 47(SUPPL.1):18-23.
5. Zhang G, Li Z, Han Q, et al (2011) Altered TNF-α and IFN-γ levels associated with PD1 but not TNFA polymorphisms in patients with chronic HBV infection. Infect Genet Evol 11(7):1624-30.
6. Ferreira Sda C, Chachá SG, Souza FF, et al (2015) IL-18, TNF, and IFNγ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury. J Med Virol 87(10):1689-96.
7. Kim YJ, Lee HS, Yoon JH, et al (2003) Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. Hum Mol Genet 12(19):2541-6.
8. Lu LP, Li XW, Liu Y, et al (2004) Association of -238G/A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population. World J Gastroenterol 10(12):1810-4.
9. Talaat RM, Abdelkhalek MS, El-Maadawy EA, Abdel-Mageed WS, El-Shenawy SZ, Osman MA (2017) Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B virus infection in Egyptians. Hum Immunol 78(11-12):739-46.
10. Fletcher GJ, Samuel P, Christdas J, et al (2011) Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population. Genes Immun 12(7):552-8.
11. Sghaier I, Zidi S, Mouelhi L, et al (2015) The relationship between TNF alpha gene polymorphisms (-238/308), TNF RII VNTR (p75) and outcomes of hepatitis B virus infection in Tunisian population. Gene 568(2):140-5.
12. Xia Q, Zhou L, Liu D, Chen Z, Chen F (2011) Relationship between TNF-<alpha> gene promoter polymorphisms and outcomes of hepatitis B virus infections: a meta-analysis. PLoS One 10;6(5).
13. Jin YJ, Lee D, Chung YH, et al (2015) Tumor necrosis factor-alpha gene polymorphism associated with development of hepatitis B virus-associated hepatocellular carcinoma. J Clin Gastroenterol 49(8):e76-81.
14. Tsuchiya N, Tokushige K, Yamaguchi N et al (2004) Influence of TNF gene polymorphism in patients with acute and fulminant hepatitis. J Gastroenterol 39(9):859-66.
15. Liu W, Wei H, Liang S, Zhang J, Sun R, Tian Z (2004) A balanced expression of two chains of heterodimer protein, the human interleukin-12, improves high-level expression of the protein in CHO cells. Biochem Biophys Res Commun 313(2):287-93.
16. Zheng Y, Wang M, Tian T, et al (2017) Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta-analysis. Oncotarget 8(18):29795-807.
17. Yuzhalin AE, Kutikhin AG (2012) Interleukin-12: clinical usage and molecular markers of cancer susceptibility. Growth Factors 30(3):176-91.
18. Liu L, Xu Y, Liu Z, et al (2011) IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 128(7):1692-6.
19. Grzegorzewska AE, Wobszal PM, Sowińska A, Mostowska A, Jagodziński PP (2013) Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection. Mol Biol Rep 40(12):6899-911.
20. Tau G, Rothman P (1999) Biologic functions of the IFN-gamma receptors. Allergy 54(12):1233-51.
21. Boehm U, Klamp T, Groot M, Howard JC (1997) Cellular responses to interferon-γ. Annu Rev Immunol 15(1):749-95.
22. Wei Y, Tian Q, Li L, Zhang D (2016) Association between IFN-γ genetic polymorphisms and susceptibility to hepatitis B virus infection: A meta-analysis. Ann Hum Biol 43(6):527-36.
23. Naghizadeh MS, Naseri M, Fereidouni M, et al (2018) Single nucleotide polymorphism of the interferon-γ gene (IFN-γ +874 T/A) and the prognosis of hepatitis B infection. J Med Microbiol Infect Dis 6(2-3):43-47.
24. Sun Y, Lu Y, Xie L, Deng Y, Li S, Qin X (2015) Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population. Cancer Cell Int 31;15:35.
25. Ji L, Zeng X, Li L, Qiu X, Chen S, Yu H (2011) Interaction between the single-nucleotide polymorphism of DNA repair gene hOGG1 and HBV infection and its susceptibility to hepatocellular carcinoma. Wei Sheng Yan Jiu 40(6):705-8.
26. Liu Y, Guo XH, Du T, et al (2005) Association of TNFA polymorphisms with the outcomes of HBV infection. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;22(4):406-10.
27. Park JS, Cheong JY, Kang JK, et al (2007) Association of interleukin-12 gene polymorphism with persistence of hepatitis B virus infection and hepatocellular carcinoma. Korean J Gastroenterol 50(5): 313-8.
28. Tan A, Gao Y, Yao Z, et al (2016) Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population. Tumour Biology 37(5):6343-8.
29. Chen X, Han S, Wang S, et al (2009) Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res. 1;15(1):400-5.
30. Ghasemian N, Shahbazi M (2016) Interferon gamma gene polymorphism (+874 T>A) and chronic hepatitis B in the Population of Gorgan, North Eastern Iran. Jundishapur J Microbiol 9(8):e33639.
31. Al Kadi M, Monem F (2017) Polymorphism of IFN-γ (+874 T/A) in Syrian patients with chronic hepatitis B. Gastroenterol Hepatol Bed Bench 10(1):34-38.
32. Ji L, Zeng X, Li L, Qiu X, Chen S, Yu H (2011) Interaction between the single-nucleotide polymorphism of DNA repair gene hOGG1 and HBV infection and its susceptibility to hepatocellular carcinoma. Wei Sheng Yan Jiu 40(6):705-8.
33. Gao QJ, Xie JX, Wang LM, Zhou Q, Zhang SY (2017) Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study. BMJ Open 23;7(8):e013279.

There are 33 citations in total.

Details

Primary Language	English
Subjects	Clinical Sciences
Journal Section	Research Articles
Authors	Gülay Börekçi 0000-0002-7879-7959 İrem Bekalp This is me 0000-0003-0681-493X Özlem Kandemir This is me 0000-0002-2602-5826 Ayşegül Çetinkaya This is me 0000-0001-5145-5118 Gülhan Orekici Temel 0000-0002-2835-6979 Nurcan Aras 0000-0002-3227-1150
Project Number	Project no: 2015-AP4-1203
Publication Date	December 31, 2020
Published in Issue	Year 2020 Volume: 5 Issue: 4

Cite

APA	Börekçi, G., Bekalp, İ., Kandemir, Ö., Çetinkaya, A., et al. (2020). Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations. Journal of Immunology and Clinical Microbiology, 5(4), 123-132.
AMA	Börekçi G, Bekalp İ, Kandemir Ö, Çetinkaya A, Orekici Temel G, Aras N. Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations. J Immunol Clin Microbiol. December 2020;5(4):123-132.
Chicago	Börekçi, Gülay, İrem Bekalp, Özlem Kandemir, Ayşegül Çetinkaya, Gülhan Orekici Temel, and Nurcan Aras. “Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations”. Journal of Immunology and Clinical Microbiology 5, no. 4 (December 2020): 123-32.
EndNote	Börekçi G, Bekalp İ, Kandemir Ö, Çetinkaya A, Orekici Temel G, Aras N (December 1, 2020) Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations. Journal of Immunology and Clinical Microbiology 5 4 123–132.
IEEE	G. Börekçi, İ. Bekalp, Ö. Kandemir, A. Çetinkaya, G. Orekici Temel, and N. Aras, “Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations”, J Immunol Clin Microbiol, vol. 5, no. 4, pp. 123–132, 2020.
ISNAD	Börekçi, Gülay et al. “Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations”. Journal of Immunology and Clinical Microbiology 5/4 (December 2020), 123-132.
JAMA	Börekçi G, Bekalp İ, Kandemir Ö, Çetinkaya A, Orekici Temel G, Aras N. Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations. J Immunol Clin Microbiol. 2020;5:123–132.
MLA	Börekçi, Gülay et al. “Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations”. Journal of Immunology and Clinical Microbiology, vol. 5, no. 4, 2020, pp. 123-32.
Vancouver	Börekçi G, Bekalp İ, Kandemir Ö, Çetinkaya A, Orekici Temel G, Aras N. Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN- γ Gene Polymorphisms and Chronic Hepatitis B in Turkish Populations. J Immunol Clin Microbiol. 2020;5(4):123-32.

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