Role of signal transducer, and activator of the transcription 4 (STAT4) gene polymorphism as predictive marker for type-1 autoimmune hepatitis

Ahmed Abbas Hasan; Hasan Raheem Khudhur; Alaa K. Hameed; Saif M. Abed

doi:10.53730/ijhs.v6nS5.10210

Authors

Ahmed Abbas Hasan Department of laboratory sciences, College of Pharmacy, University of Kerbala, Kerbala, Iraq
Hasan Raheem Khudhur College of Education for Pure Science, Al-Muthanna University, Iraq
Alaa K. Hameed College of Health and Medical Techniques, Sawa University
Saif M. Abed Department of Medical laboratories, College of Medical and Health Techniques, Sawa University, Iraq

Keywords:

Autoimmune hepatitis type I, gene Polymorphism, transcription 4 (STAT4)

Abstract

Introduction: Autoimmune hepatitis (AIH) is one of autoimmune disorder with complex pathophysiology. Many genes involved in lethal autoimmune hepatitis disorder including STAT4 gene. The aim of this study is to determine STAT4 gene polymorphisms and relation of SNPs with disease severity among AIH patients. Method: One hundred AIH patient which diagnosed by clinically, ANA and ASMA and 100 control age matched healthy children were enrolled in this study. Patients' blood samples (5mL) were taken and split into two tubes, one tube used for immunological and clinical parameters and the second containing EDTA for PCR analysis. The first tubes were then left at room temperature for 10 minutes before being centrifuged (3500 rpm). After that, the serum was isolated the both tubes stored at -70°C until analysis, biochemical parameters were measured in full automated biochemistry analyzer while, IgG, ANA and ASMA was investigated using the enzyme-linked immunosorbent assay (ELISA) commercially available kits (Bioneer, Korea), while the STAT4 (rs7574865, rs7582694) gene was investigated using RFLP PCR How, and the commercially available kits (Bioneer, Korea).

Downloads

Download data is not yet available.

References

Aizawa, Y. and Hokari, A., 2017. Autoimmune hepatitis: current challenges and future prospects. Clinical and experimental gastroenterology, 10, p.9.

Begovich, A. B., V. E. Carlton, L. A. Honigberg, S. J. Schrodi, A. P. Chokkalingam, H. C. Alexander, K. G. Ardlie, Q. Huang, A. M. Smith and J. M. Spoerke.2004. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. The American Journal of Human Genetics. 75 (2):330-337.

Behairy, O. G., Alnady, N. M., Mohammed, S. A., & Ibrahim, W. A. .2021. STAT4 Gene Polymorphism in Children with Type-1 Autoimmune Hepatitis. Journal of Gastroenterology and Hepatology Research, 10(3), 3504-3509.

Chaouali, M., V. Fernandes, E. Ghazouani, L. Pereira and R. Kochkar.2018. Association of STAT4, TGFβ1, SH2B3 and PTPN22 polymorphisms with autoimmune hepatitis. Experimental and molecular pathology. 105 (3):279-284.

Czaja, A. J. and M. P. Manns.2010. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology. 139 (1):58-72. e54.

Deneau, M., M. K. Jensen, J. Holmen, M. S. Williams, L. S. Book and S. L. Guthery.2013. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology. 58 (4):1392-1400.

Ferrari, R., Pappas, G., Agostinelli, D., Muratori, P., Muratori, L., Lenzi, M., ... & Bianchi, F. B. 2004. Type 1 autoimmune hepatitis: patterns of clinical presentation and differential diagnosis of the ‘acute’type. Qjm, 97(7), 407-412.‏

Floreani, A., R. Liberal, D. Vergani and G. Mieli-Vergani.2013. Autoimmune hepatitis: contrasts and comparisons in children and adults–a comprehensive review. Journal of autoimmunity. 46 7-16.

Hinks, A., A. Barton, S. John, I. Bruce, C. Hawkins, C. E. Griffiths, R. Donn, W. Thomson, A. Silman and J. Worthington.2005. Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis & Rheumatism. 52 (6):1694-1699.

Li, X., Chen, H., Cai, Y., Zhang, P., & Chen, Z. 2017. Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children. Oncotarget, 8(37), 60933., rs2476601

Liang, Y.L., Wu, H., Shen, X., Li, P.Q., Yang, X.Q., Liang, L., Tian, W.H., Zhang, L.F. and Xie, X.D., 2012. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis. Molecular biology reports, 39(9), pp.8873-8882.

Orozco, G., E. Sánchez, M. A. González‐Gay, M. A. López‐Nevot, B. Torres, R. Cáliz, N. Ortego‐Centeno, J. Jiménez‐Alonso, D. Pascual‐Salcedo and A. Balsa.2005. Association of a functional single‐nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 52 (1):219-224.

Orru, V., S. J. Tsai, B. Rueda, E. Fiorillo, S. M. Stanford, J. Dasgupta, J. Hartiala, L. Zhao, N. Ortego-Centeno and S. D’Alfonso.2009. A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Human molecular genetics. 18 (3):569-579.

Özdoğan, O. and Yaraş, S., 2020. Our Autoimmune Hepatitis Patients: Single Center Experience. Istanbul Medical Journal, 21(2).

Pohl, A., Behling, C., Oliver, D., Kilani, M., Monson, P., & Hassanein, T. 2001. Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection. The American journal of gastroenterology, 96(11), 3142-3146.‏

Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007;357:977–86.

Sugiura, T., Kawaguchi, Y., Goto, K., Hayashi, Y., Tsuburaya, R., Furuya, T., Gono, T., Nishino, I. and Yamanaka, H., 2012. Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis in a Japanese population. Annals of the rheumatic diseases, 71(10), pp.1646-1650.

Taylor KE, Remmers EF, Lee AT, Ortmann WA, Plenge RM, Tian C, Chung SA, Nititham J, Hom G, Kao AH, Demirci FY, Kamboh MI, Petri M, et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet. 2008;4:e1000084.

Tong G, Zhang X, Tong W, Liu Y. Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis. Hum Immunol. 2013;74:586–92..

Umemura, T., Y. Katsuyama, K. Yoshizawa, T. Kimura, S. Joshita, M. Komatsu, A. Matsumoto, E. Tanaka and M. Ota.2014. Human leukocyte antigen class II haplotypes affect clinical characteristics and progression of type 1 autoimmune hepatitis in Japan. PLoS One. 9 (6):e100565.

Watford, W.T., Hissong, B.D., Bream, J.H., Kanno, Y., Muul, L. and O'Shea, J.J., 2004. Signaling by IL‐12 and IL‐23 and the immunoregulatory roles of STAT4. Immunological reviews, 202(1), pp.139-156

Dwijaya, A., & Atmaja, M. H. S. (2022). Clinical and imaging findings of klippel-trenaunay syndrome: A case report. International Journal of Health & Medical Sciences, 5(1), 145-149. https://doi.org/10.21744/ijhms.v5n1.1860

Xu, M., Morishima, N., Mizoguchi, I., Chiba, Y., Fujita, K., Kuroda, M., Iwakura, Y., Cua, D.J., Yasutomo, K., Mizuguchi, J. and Yoshimoto, T., 2011. Regulation of the development of acute hepatitis by IL‐23 through IL‐22 and IL‐17 production. European journal of immunology, 41(10), pp.2828-2839.

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2022). Post-pandemic health and its sustainability: Educational situation. International Journal of Health Sciences, 6(1), i-v. https://doi.org/10.53730/ijhs.v6n1.5949

Xu, M., N. Morishima, I. Mizoguchi, Y. Chiba, K. Fujita, M. Kuroda, Y. Iwakura, D. J. Cua, K. Yasutomo and J. Mizuguchi.2011. Regulation of the development of acute hepatitis by IL‐23 through IL‐22 and IL‐17 production. European journal of immunology. 41 (10):2828-2839.

Yang, C., H. Mai, J. Peng, B. Zhou, J. Hou and D. Jiang.2020. STAT4: an immunoregulator contributing to diverse human diseases. International journal of biological sciences. 16 (9):1575.