Role of Interferon-Gamma +874 A/T Single-Nucleotide Polymorphism and Tuberculosis Susceptibility of Pediatric Population in North Sumatera, Indonesia

Authors

  • Rini Savitri Daulay Department of Child Health, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Rina Amalia C. Saragih Department of Child Health, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Ridwan Muchtar Daulay Department of Child Health, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Ratna Akbari Ganie Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Gino Tann Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Bambang Supriyatno Department of Child Health, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7441

Keywords:

Tuberculosis, Interferon-gamma, Single-nucleotide polymorphism, 874 A/T, Pediatric, Indonesia

Abstract

BACKGROUND: Tuberculosis (TB) remains to be a leading cause of morbidity and mortality worldwide. The immune defense against Mycobacterium tuberculosis (M. tuberculosis) is complicated. Interferon gamma (IFN-g) is the main cytokine involved in the immune response of TB. To date, the role of +874 A/T single nucleotide polymorphism (SNP) and TB disease susceptibility continue to be controversial.

OBJECTIVES: The aim of this study was to investigate the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia

METHODS:  A case control study was conducted in Medan and Batubara, North Sumatera, Indonesia from January to December 2016. A total of 51 children with TB and 51 healthy controls were enrolled in this study. Subjects were 2 months to 14 years old age children diagnosed with TB and written informed consent from the parents or the caregivers to participate. Subjects were withdrawn from the study when immunodeficiency condition was found or suffered from other infection disease. DNA samples were obtained from all of the subjects. +874 A/T SNP was identified by performing the amplification refractory mutational system - polymerase chain reaction (ARMS-PCR) method. IFN-g levels were measured by using human enzyme-linked immunosorbent assay/ELISA. Data analysis was performed using chi square and Mann Whitney test. p value <0.05 was considered significant.

RESULTS: The result of this study reveals the presence of AA, AT and TT genotype in TB patients were 31 (60.8%), 20 (39.2%) and 0 (0%); respectively (p=0.023). Significant decreased production of IFN-g levels (p=0.042) were found in TB patients 9.41 (1.10 – 28.06) pg/ml.

CONCLUSION: Our study demonstrated significant evidence of the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia predominantly AA genotype. Significant decreased production of IFN-g reported among pediatric TB.

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References

World Health Organization. Global Tuberculosis Report. Geneva: World Health Organization; 2020. Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports [Last accessed on 2021 Sep 10].

Azad A, Sadee W, Schlesinger L. Innate immune gene polymorphisms in tuberculosis. Infect Immun. 2012;80(10):3343-59. http://doi.org/10.1128/IAI.00443-12 PMid:22825450 DOI: https://doi.org/10.1128/IAI.00443-12

Cavalcanti Y, Brelaz M, Lemoine Neves J, Ferraz J, Pereira V. Role of TNF-alpha, IFN-gamma, and IL-10 in the development of pulmonary tuberculosis. Pulm Med. 2012;2012:745483. http://doi.org/10.1155/2012/745483 PMid:23251798 DOI: https://doi.org/10.1155/2012/745483

Weiss G, Schaible U. Macrophage defense mechanisms against intracellular bacteria. Immunol Rev. 2015;264(1):182-203. http://doi.org/10.1111/imr.12266 PMid:25703560 DOI: https://doi.org/10.1111/imr.12266

Pravica V, Perrey C, Stevens A, Lee J, Hutchinson I. A single nucleotide polymorphism in the first intron of the human IFN-γ gene. Hum Immunol. 2000;61(9):863-6. http://doi.org/10.1016/s0198-8859(00)00167-1 PMid:11053629 DOI: https://doi.org/10.1016/S0198-8859(00)00167-1

Möller M, Hoal E. Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis. 2010;90(2):71-83. http://doi.org/10.1016/j.tube.2010.02.002 PMid:20206579 DOI: https://doi.org/10.1016/j.tube.2010.02.002

Singh D, Bagam P, Sahoo M, Batra S. Immune-related gene polymorphisms in pulmonary diseases. Toxicology. 2017;383:24-39. http://doi.org/10.1016/j.tox.2017.03.020 PMid:28366820 DOI: https://doi.org/10.1016/j.tox.2017.03.020

Shen C, Jiao W, Feng W, Wu X, Xiao J, Miao Q, et al. IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population. Mol Biol Rep. 2013;40(9):5477-82. http://doi.org/10.1007/s11033-013-2647-7 PMid:23737189 DOI: https://doi.org/10.1007/s11033-013-2647-7

Selma W, Harizi H, Bougmiza I, Hannachi N, Kahla I, Zaieni R, et al. Interferon gamma +874T/A polymorphism is associated with susceptibility to active pulmonary tuberculosis development in Tunisian patients. DNA Cell Biol. 2011;30(6):379-87. http://doi.org/10.1089/dna.2010.1157 PMid:21332391 DOI: https://doi.org/10.1089/dna.2010.1157

Mosaad Y, Soliman O, Tawhid Z, Sherif D. Interferon-gamma +874 T/A and interleukin-10-1082 A/G single nucleotide polymorphism in Egyptian children with tuberculosis. Scand J Immunol. 2010;72(4):358-64. http://doi.org/10.1111/j.1365-3083.2010.02426.x PMid:20883321 DOI: https://doi.org/10.1111/j.1365-3083.2010.02426.x

Etokebe G, Bulat-Kardum L, Johansen M, Knezevic J, Balen S, Matakovic-Mileusnic N, et al. Interferon-gamma gene (T874A and G2109A) polymorphisms are associated with microscopy-positive tuberculosis. Scand J Immunol. 2006;63(2):136-41. http://doi.org/10.1111/j.1365-3083.2005.01716.x PMid:16476013 DOI: https://doi.org/10.1111/j.1365-3083.2005.01716.x

Amim L, Pacheco A, Fonseca-Costa J, Loredo C, Rabahi M, Melo M, et al. Role of IFN-γ +874 T/A single nucleotide polymorphism in the tuberculosis outcome among Brazilians subjects. Mol Biol Rep. 2007;35(4):563-6. http://doi.org/10.1007/s11033-007-9123-1 PMid:17682837 DOI: https://doi.org/10.1007/s11033-007-9123-1

Lee S, Chuang T, Huang H, Lee K, Chen T, Kao Y, et al. Interferon gamma polymorphisms associated with susceptibility to tuberculosis in a Han Taiwanese population. J Microbiol Immunol Infect. 2015;48(4):376-80. http://doi.org/10.1016/j.jmii.2013.11.009 PMid:24529854 DOI: https://doi.org/10.1016/j.jmii.2013.11.009

Ding S, Li L, Zhu X. Polymorphism of the interferon-γ gene and risk of tuberculosis in a Southeastern Chinese population. Hum Immunol. 2008;69(2):129-33. http://doi.org/10.1016/j.humimm.2007.11.006 PMid:18361939 DOI: https://doi.org/10.1016/j.humimm.2007.11.006

Naderi M, Hashemi M, Taheri M, Pesarakli H, Eskandari- Nasab E, Bahari G. CD209 promoter 336 A/G (rs4804803) polymorphism is associated with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran. J Microbiol Immunol Infect. 2014;47(3):171-5. http://doi.org/10.1016/j.jmii.2013.03.013 PMid:23751770 DOI: https://doi.org/10.1016/j.jmii.2013.03.013

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Published

2021-12-12

How to Cite

1.
Daulay RS, Saragih RAC, Daulay RM, Ganie RA, Tann G, Supriyatno B. Role of Interferon-Gamma +874 A/T Single-Nucleotide Polymorphism and Tuberculosis Susceptibility of Pediatric Population in North Sumatera, Indonesia. Open Access Maced J Med Sci [Internet]. 2021 Dec. 12 [cited 2024 Nov. 21];9(A):1057-60. Available from: https://oamjms.eu/index.php/mjms/article/view/7441