Association Of IL-4 Gene Polymorphism with Serum Ige And Eosinophil Levels in Asthma Patients

Authors

  • Hadeel S. Hadi College of Science, University of Al-Qadisiyah, Al-Qadisiyah, Iraq

Keywords:

IgE, Eosinophils, Il-4, Asthma, Gene Polymorphism

Abstract

Asthma represents a chronic airway inflammatory disease with a Th2-cell polarization as the major design of immune response, and interleukin-4 (IL-4) is pivotal in IgE production and eosinophilia. Polymorphisms in the IL-4 gene can alter an individual's susceptibility to asthma and its associated immunological markers. The purpose of this study was to determine if there was a relationship between the genotypic distribution in 2 IL-4 gene polymorphic sites and the asthma IgE level and the peripheral eosinophil count. A cross-sectional case-control study was carried out at Al-Sadr Medical City, Najaf, Iraq from March to December 2025, that included 98 asthmatic patients who were diagnosed by the Global Initiative for Asthma (GINA) guidelines and 52 healthy controls age- and sex-matched. Demographic and clinical information was obtained with the help of structured questionnaires. Serum total IgE were quantified by ELISA, eosinophils were determined with an automated hematology analyzer and the IL-4 gene polymorphism was investigated using PCR-RFLP. Serum IgE levels (310.6 ± 118.4 IU/mL vs. 142.3 ± 64.7 IU/mL, P < 0.002) and eosinophil counts (468.2 ±152.6 vs.286·9 _. 104.s cellsip1L, :P<0T03,) were significantly higher in asthmatics than in control subjects; The IL-4 T allele, and TC and TT genotypes were significantly higher in asthmatic patients than in control individuals. In addition, the T allele and TT+TC genotype were significantly correlated with higher levels of IgE and eosinophilia in asthmatics. In summary, our results demonstrate that the IL-4 gene polymorphism is associated with asthmatic susceptibility and important immunological mechanisms of asthma such as total IgE production and eosinophilic inflammation. These findings reinforce the contribution of genetic variation at IL-4 to the immunopathogenesis of asthma, and propose that IL-4 might be useful as a genetic and immunological marker for both asthma susceptibility and phenotype stratification.

References

Al-Hachamy, A. H., & Al-Saadi, A. (2015). Association of interleukin-4 (IL4) gene polymorphisms with asthma. Research Journal of Fisheries and Hydrobiology, 10(9), 8–10.

Bateman, E. D., Hurd, S. S., Barnes, P. J., Bousquet, J., Drazen, J. M., FitzGerald, J. M., Gibson, P., Ohta, K., O'Byrne, P., Pedersen, S. E., Pizzichini, E., Sullivan, S. D., Wenzel, S. E., & Zar, H. J. (2008). Global strategy for asthma management and prevention: GINA executive summary. The European respiratory journal, 31(1), 143–178. https://doi.org/10.1183/09031936.00138707

Chiang, C. H., Tang, Y. C., Lin, M. W., & Chung, M. Y. (2007). Association between the IL-4 promoter polymorphisms and asthma or severity of hyperresponsiveness in Taiwanese. Respirology (Carlton, Vic.), 12(1), 42–48. https://doi.org/10.1111/j.1440-1843.2006.00960.x

Cui, T., Wu, J., Pan, S., & Xie, J. (2003). Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma. Clinical chemistry and laboratory medicine, 41(7), 888–892. https://doi.org/10.1515/CCLM.2003.134

Fahy J. V. (2015). Type 2 inflammation in asthma--present in most, absent in many. Nature reviews. Immunology, 15(1), 57–65. https://doi.org/10.1038/nri3786

Hinks, T. S. C., Brown, T., Lau, L. C. K., Rupani, H., Barber, C., Elliott, S., Ward, J. A., Ono, J., Ohta, S., Izuhara, K., Djukanović, R., Kurukulaaratchy, R. J., Chauhan, A., & Howarth, P. H. (2016). Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. The Journal of allergy and clinical immunology, 138(1), 61–75. https://doi.org/10.1016/j.jaci.2015.11.020

Imani, D., Eslami, M. M., Anani-Sarab, G., Aliyu, M., Razi, B., & Rezaei, R. (2020). Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications. BMC medical genetics, 21(1), 232. https://doi.org/10.1186/s12881-020-01169-w

Junttila I. S. (2018). Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes. Frontiers in immunology, 9, 888. https://doi.org/10.3389/fimmu.2018.00888

Li, Y., Wu, B., Xiong, H., & Zhu, C. (2021). Association between IL-4 −590C/T polymorphism and asthma susceptibility: A meta-analysis. Allergy, Asthma & Clinical Immunology, 17(1), 58. https://doi.org/10.1186/s13223-021-00554-9

Liu, T., Yin, W., Luo, L., Wu, Y., Qin, S., & Qin, X. (2022). Association between Interleukin-4-590C>T Polymorphism and the Susceptibility to Asthma: A Meta-Analysis of Case-Control Study. Journal of healthcare engineering, 2022, 1712715. https://doi.org/10.1155/2022/1712715 (Retraction published J Healthc Eng. 2023 Oct 4;2023:9876540. doi: 10.1155/2023/9876540

Matucci, A., Vultaggio, A., Maggi, E., & Kasujee, I. (2018). Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question?. Respiratory research, 19(1), 113. https://doi.org/10.1186/s12931-018-0813-0

Meyers, D. A., Bleecker, E. R., Holloway, J. W., & Holgate, S. T. (2014). Asthma genetics and personalised medicine. The Lancet. Respiratory medicine, 2(5), 405–415. https://doi.org/10.1016/S2213-2600(14)70012-8

Ober, C., & Yao, T. C. (2011). The genetics of asthma and allergic disease: a 21st century perspective. Immunological reviews, 242(1), 10–30. https://doi.org/10.1111/j.1600-065X.2011.01029.x

Papi, A., Brightling, C., Pedersen, S. E., & Reddel, H. K. (2018). Asthma. Lancet (London, England), 391(10122), 783–800. https://doi.org/10.1016/S0140-6736(17)33311-1

Paul, W. E., & Zhu, J. (2010). How are T(H)2-type immune responses initiated and amplified?. Nature reviews. Immunology, 10(4), 225–235. https://doi.org/10.1038/nri2735

Shirkani, A., Mansouri, A., Farid Hosseini, R., Jabbari Azad, F., Alsadat Mahmoudian, R., Montazer, M., Samimi, A., Momtazi-Borojeni, A. A., Abbaszadegan, M. R., & Gholamin, M. (2019). The Role of Interleukin-4 and 13 Gene Polymorphisms in Allergic Rhinitis: A Case Control Study. Reports of biochemistry & molecular biology, 8(2), 111–118.

Tavakkol Afshari, J., Farid Hosseini, R., Hosseini Farahabadi, S., Heydarian, F., Boskabady, M. H., Khoshnavaz, R., Razavi, A., Ghayoor Karimiani, E., & Ghasemi, G. (2007). Association of the expression of IL-4 and IL-13 genes, IL-4 and IgE serum levels with allergic asthma. Iranian journal of allergy, asthma, and immunology, 6(2), 67–72.

Tiotiu A. (2018). Biomarkers in asthma: state of the art. Asthma research and practice, 4, 10. https://doi.org/10.1186/s40733-018-0047-4

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Published

2026-01-30