Interleukin-18 cytokine gene polymorphism 137G/C (rs187238) and susceptibility to tuberculosis in north India
Abstract
Tuberculosis (TB) regained its position globally as the leading cause of mortality from a single infectious agent after being surpassed by COVID-19 for 3 years consecutively. Host genetic factors, particularly cytokine gene polymorphisms, play a significant role in influencing susceptibility to TB. Interleukin-18 (IL18) is a proinflammatory cytokine involved in immune regulation against Mycobacterium tuberculosis. This study aimed to evaluate the association of IL18 gene polymorphism (rs187238) with susceptibility to TB and its effect on serum IL18 levels in a north Indian population. A case-control study was conducted with 100 newly diagnosed TB patients (pulmonary and extrapulmonary) and 100 age- and gender-matched healthy controls. Serum IL18 levels were measured using sandwich enzyme-linked immunosorbent assay, and the IL18 gene polymorphism at rs187238 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between IL18 polymorphism, TB susceptibility, and serum IL18 levels was statistically evaluated. Mean serum IL18 levels were significantly elevated in TB patients (400.42±149.58 pg/mL) compared to controls (96.05±40.67 pg/mL; p<0.01). The distribution of IL18 genotypes showed that individuals with GC/CC genotypes had a significantly lower risk of developing TB compared to the GG genotype [odds ratio (OR)=0.31; 95% confidence interval (CI)=0.20-0.88; p=0.0167]. Additionally, the C allele conferred a protective effect against TB (OR=0.33; 95% CI=0.22-0.51; p<0.0001). Serum IL18 concentrations varied significantly with genotype, with the highest levels observed in CC genotype carriers in both cases and controls (p<0.01). Thus, our study suggests that IL18 polymorphism at rs187238 significantly influences susceptibility to TB in the north Indian population. The C allele and GC/CC genotypes appear to confer a protective effect, possibly through modulation of IL18 serum levels. IL18 rs187238 polymorphism may serve as an independent predictive marker for TB risk, though larger studies are recommended for validation.
Ethics Approval
Ethical clearance was obtained from the Institutional Ethics Committee, VMMC, and Safdarjung Hospital, New Delhi, with serial no. IEC/VMMC/SJH/THESIS/06/2022/CC-65 dated 11 July 2022.
References
- United Nations. Sustainable Development Goals. 2024. Available from: ?
- WHO. Global tuberculosis report 2024. Available from: https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2024.
- Ministry of Health and Family Welfare, Government of India. India TB report 2024. Available from: https://tbcindia.mohfw.gov.in/wp-content/uploads/2024/10/TB-Report_for-Web_08_10-2024-1.pdf.
- Andrews JR, Noubary F, Walensky RP, et al. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis 2012;54:784-91. DOI: https://doi.org/10.1093/cid/cir951
- WHO. Global tuberculosis report 2016. Available from: https://iris.who.int/bitstream/handle/10665/250441/9789241565394-eng.pdf?sequence=1.
- Song CH, Lee JS, Nam HH, et al. IL-18 production in human pulmonary and pleural tuberculosis. Scand J Immunol 2002;56:611-8. DOI: https://doi.org/10.1046/j.1365-3083.2002.01143.x
- Zhen LB, Sun YP, Chen YY, Yin LS. IL-18 polymorphisms and tuberculosis susceptibility: a meta-analysis. Afr Health Sci 2019;19:1311-20. DOI: https://doi.org/10.4314/ahs.v19i1.2
- Banda NK, Vondracek A, Kraus D, et al. Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein. J Immunol 2003;170:2100-5. DOI: https://doi.org/10.4049/jimmunol.170.4.2100
- Heemskerk D, Caws M, Marais B, Farrar J. Tuberculosis in adults and children. London: Springer; 2015. DOI: https://doi.org/10.1007/978-3-319-19132-4
- Dima E, Koltsida O, Katsaounou P, et al. Implication of Interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD).Cytokine 2015;74:313-7. DOI: https://doi.org/10.1016/j.cyto.2015.04.008
- Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol 2013;4:289. DOI: https://doi.org/10.3389/fimmu.2013.00289
- Song CH, Lee JS, Nam HH, et al. IL-18 production in human pulmonary and pleural tuberculosis. Scand J Immunol 2002;56:611-8. DOI: https://doi.org/10.1046/j.1365-3083.2002.01143.x
- Inomata SI, Shijubo N, Kon S, et al. Circulating interleukin-18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis. Cytokine 2005;30:203-11. DOI: https://doi.org/10.1016/j.cyto.2005.01.014
- Yamada G, Shijubo N, Shigehara K, et al. Increased levels of circulating interleukin-18 in patients with advanced tuberculosis. Am J Respir Crit Care Med 2000;161:1786-9. DOI: https://doi.org/10.1164/ajrccm.161.6.9911054
- Khripko OP, Sennikova NS, Lopatnikova JA, et al. Association of single nucleotide polymorphisms in the IL-18 gene with production of IL-18 protein by mononuclear cells from healthy donors. Mediators Inflamm 2008:309721. DOI: https://doi.org/10.1155/2008/309721
- Giedraitis V, He B, Huang WX, Hillert J. Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol 2001;112:146-52. DOI: https://doi.org/10.1016/S0165-5728(00)00407-0
- Hassuna NA, Mohamed El Feky, Hussein M, et al. Interleukin-18 and interferon-γ single nucleotide polymorphisms in Egyptian patients with tuberculosis. PLoS One 2021;16:e0244949. DOI: https://doi.org/10.1371/journal.pone.0244949
- Shen L, Liang Z, Xu C, et al. Association between Interleukin-18-137G/C gene polymorphisms and tuberculosis risk in Chinese population: a meta-analysis. J Clin Cell Immunol 2017;08:514 DOI: https://doi.org/10.4172/2155-9899.1000514
- Zhen LB, Sun YP, Chen YY, Yin LS. IL-18 polymorphisms and tuberculosis susceptibility: a meta-analysis. Afr Health Sci 2019;19:1311. DOI: https://doi.org/10.4314/ahs.v19i1.2
- Cavalcante JEA, de Sousa ELH, de Oliveira Rodrigues R, et al. Interleukin-18 promoter -137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients. Clin Biochem 2020;80:1-7. DOI: https://doi.org/10.1016/j.clinbiochem.2020.03.011
- Evans J, Collins M, Jennings C, et al. The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease. Eur J Endocrinol 2007;157:633-40. DOI: https://doi.org/10.1530/EJE-07-0463
- Wu S, Wang Y, Zhang M, et al. Genetic variants in IFNG and IFNGR1 and tuberculosis susceptibility. Cytokine 2019;123:154775. DOI: https://doi.org/10.1016/j.cyto.2019.154775
Metrics
Citations and online attention from Dimensions, Altmetric and PlumX.
License
Copyright (c) 2025 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.