https://doi.org/10.4081/monaldi.2023.2594

Association of IL4RA and IL-8 polymorphism in predicting susceptibility towards tuberculosis

Early Access
Submitted: April 4, 2023
Accepted: July 5, 2023
Published: August 10, 2023
Tuberculosis, polymorphism, IL-8 +781 C/T, IL-4 RA Q576R
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PDF_early view: 236
Supplementary: 51
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Authors

Jyotish K
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Jawahar Lal Joshi
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Heena Kansal
Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India.
Vishal Chopra
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Kranti Garg
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Nidhi Girdhar
https://orcid.org/0000-0003-4690-4796
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Karan Sharma
https://orcid.org/0000-0003-1872-6136
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Rishabh Deshwal
Department of Pulmonary Medicine, Government Medical College, Tuberculosis and Chest Diseases Hospital, Patiala, India.
Siddharth Sharma
Siddharthsharma.phd@thapar.edu
Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India.

Mycobacterium tuberculosis is an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The aetiology of tuberculosis has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphism on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. PCR RFLP was performed to identify the genotype of the IL4RAQ576R and IL-8 +781C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p= 0.03) in tuberculosis. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781C/T, showed a significant association. Moreover, different combinations of the SNPS were made, and the 3 risk allele shows a significant protective role (p=0.02). There is considerable evidence which shows that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against tuberculosis, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with tuberculosis. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing tuberculosis.

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Scopus
Google Scholar
Europe PMC
Dara M, Acosta CD, Melchers NV, et al. Tuberculosis control in prisons: current situation and research gaps. Int J Infect Diss 2015;32:111-7. DOI: https://doi.org/10.1016/j.ijid.2014.12.029
Bloom BR, Small PM. The evolving relation between humans and Mycobacterium tuberculosis. N Engl J Med 1998;338:677-8. DOI: https://doi.org/10.1056/NEJM199803053381008
Antonucci G, Girardi E, Raviglione MC, et al. Risk factors for tuberculosis in HIV-lnfected persons: a prospective cohort study. JAMA 1995;274:143-8. DOI: https://doi.org/10.1001/jama.274.2.143
Chakrabartty A, Basu P, Ali KM, et al. Tuberculosis related stigma and its effect on the delay for sputum examination under the Revised National Tuberculosis Control Program in India. Indian J Tuberc 2018;65:145-51. DOI: https://doi.org/10.1016/j.ijtb.2017.08.032
Mukaida NA, Shiroo MA, Matsushima KO. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol 1989;143:1366-71. DOI: https://doi.org/10.4049/jimmunol.143.4.1366
Agarwal R, Srinivas R, Aggarwal AN, Saxena AK. Pulmonary masses in allergic bronchopulmonary aspergillosis: mechanistic explanations. Respir Care 2008;53:1744-8.
Wani RL. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. South Sudan Med J 2013;6:10-2.
North RJ, Jung YJ. Immunity to tuberculosis Annu Rev Immunol 2004;22:599-623. DOI: https://doi.org/10.1146/annurev.immunol.22.012703.104635
Jimenez-Sousa MA, López E, Fernandez-Rodríguez A, et al. Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study. BMC Med Genet 2012;13:58. DOI: https://doi.org/10.1186/1471-2350-13-58
van Crevel R, Ottenhoff TH, van der Meer JW. Innate immunity to Mycobacterium tuberculosis. Clin Microbiol Rev 2002;15:294-309. DOI: https://doi.org/10.1128/CMR.15.2.294-309.2002
Bartlett JM, Stirling D. PCR protocols. Totowa, NJ: Humana Press; 2003. DOI: https://doi.org/10.1385/1592593844
Ohrui T, Zayasu K, Sato E, et al. Pulmonary tuberculosis and serum IgE. Clin Exp Immunol 2000;122:13-5. DOI: https://doi.org/10.1046/j.1365-2249.2000.01291.x
Hershey GK, Friedrich MF, Esswein LA, et al. The association of atopy with a gain-of-function mutation in the α subunit of the interleukin-4 receptor. N Engl J Med 1997;337:1720-5. DOI: https://doi.org/10.1056/NEJM199712113372403
Moreno O, González CI, Saaibi DL, et al. Polymorphisms in the IL4 and IL4RA genes in Colombian patients with rheumatoid arthritis. J Rheumatol 2007;34:36-42.
Howard TD, Koppelman GH, Xu J, et al. Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Am J Hum Gen 2002;70:230-6. DOI: https://doi.org/10.1086/338242
Hegab AE, Sakamoto T, Saitoh W, et al. Polymorphisms of IL4, IL13, and ADRB2 genes in COPD. Chest 2004;126:1832-9. DOI: https://doi.org/10.1378/chest.126.6.1832
Li L, Li Y, Zeng X, et al. Role of interleukin-4 genetic polymorphisms and environmental factors in the risk of asthma in children. Genet Mol Res 2016;15:534-43. DOI: https://doi.org/10.4238/gmr15048873
Beghé B, Barton S, Rorke S, et al. Polymorphisms in the interleukin‐4 and interleukin‐4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population. Clin Exp Allergy 2003;33:1111-7. DOI: https://doi.org/10.1046/j.1365-2222.2003.01731.x
Rosa-Rosa L, Zimmermann N, Bernstein JA, et al. The R576 IL-4 receptor α allele correlates with asthma severity. J Allergy Clin Immunol 1999;104:1008-14. DOI: https://doi.org/10.1016/S0091-6749(99)70082-5
Hafez SF, Amer OT, Mostafa OA, Samy WM. Polymorphism RS2227306 in the interleukin 8 gene and its relation to bronchial asthma. Egypt J Hospital Med 2021;86:50-3. DOI: https://doi.org/10.21608/ejhm.2021.209977
Rook GA, Hernandez-Pando R, Dheda K, Seah GT. IL-4 in tuberculosis: implications for vaccine design. Trends Immunol 2004;25:483-8. DOI: https://doi.org/10.1016/j.it.2004.06.005
Ma X, Reich RA, Wright JA, et al. Association between interleukin-8 gene alleles and human susceptibility to tuberculosis disease. J Infect Dis 2003;188:349-55. DOI: https://doi.org/10.1086/376559
Krupa A, Fol M, Dziadek BR, et al. Binding of CXCL8/IL-8 to Mycobacterium tuberculosis modulates the innate immune response. Mediators Inflamm 2015;2015:124762. DOI: https://doi.org/10.1155/2015/124762
Selvaraj P, Anand SP, Jawahar MS, et al. Promoter polymorphism of IL-8 gene and IL-8 production in pulmonary tuberculosis. Curr Sci 2006:952-4.
Chen J, Ma A. Associations of polymorphisms in interleukins with tuberculosis: Evidence from a meta-analysis. Immunol Lett 2020;217:1-6. DOI: https://doi.org/10.1016/j.imlet.2019.10.012
Walia HK, Sharma P, Singh N, Sharma S. Synergistic polymorphic interactions of phase II metabolizing genes and their association toward lung cancer susceptibility in North Indians. Int J Environ Health Res 2022. Online ahead of print. DOI: https://doi.org/10.1080/09603123.2022.2133095

Ethics Approval

Ethics Committee of Baba Farid Medical College (docket number BFUHS/2K21p-TH/14858)

How to Cite

K, Jyotish, Jawahar Lal Joshi, Heena Kansal, Vishal Chopra, Kranti Garg, Nidhi Girdhar, Karan Sharma, Rishabh Deshwal, and Siddharth Sharma. 2023. “Association of <em>IL4RA</em> and <em>IL-8</em> Polymorphism in Predicting Susceptibility towards Tuberculosis”. Monaldi Archives for Chest Disease, August. https://doi.org/10.4081/monaldi.2023.2594.
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