Role of FOXP3 (rs3761548) Polymorphism in Modulating FOXP3 Protein Level in Iraqi Patients with Thyroid Disorder

Authors

  • Basma Ahmed Muayad Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0004-3676-9329
  • Hamsa Ahmed Jassim Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0005-6421-669X

DOI:

https://doi.org/10.54133/ajms.v8i1.1684

Keywords:

Forkhead box p3 (FOXP3), Polymorphism, rs3761548, Thyroid disorder

Abstract

Background: Thyroid disorders are a major clinical concern that negatively impacts the thyroid gland. Thyroid issues have been connected to the FOXP3 gene, which is an important immune system regulator. FOXP3 protein levels can be affected by genetic differences, which may impair regulatory T-cell activity and exacerbate immunological abnormalities. Objectives: To investigate the influence of FOXP3 gene polymorphisms on circulating FOXP3 protein levels and their association with thyroid dysfunction. Methods: This study included 100 patients with thyroid disorders and 50 healthy controls. Thyroid function was assessed by measuring serum T3, T4, and TSH levels using a Cobas analyzer. Serum FOXP3 protein levels were quantified by ELISA. Genomic DNA was extracted and analyzed for FOXP3 gene variations using PCR and sequencing. Results: No significant differences were observed in serum T3 and T4 levels between patients and controls. However, TSH levels were significantly elevated in the patient group. Serum FOXP3 levels were significantly lower in patients compared to controls. The distribution of the three FOXP3 gene genotypes (AA, AC, and CC) did not differ significantly between patients and controls. Individuals with the heterozygous (AC) genotype exhibited significantly higher serum FOXP3 levels compared to the other two genotypes. Conclusions: Individuals with thyroid disorders had reduced levels of FOXP3, which may indicate an association between thyroid disease and impaired immunity. The study emphasizes the complicated interaction of genetic and environmental factors, even if it could not identify an obvious connection with the rs3761548 gene variation.

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References

Hiller-Sturmhöfel S, Bartke A. The endocrine system: an overview. Alcohol Health Res World. 1998;22(3):153–164. PMID: 15706790.

Mammen JSR, Cappola AR. Autoimmune thyroid disease in women. JAMA. 2021;325(23):2392–3. doi: 10.1001/jama.2020.22196. DOI: https://doi.org/10.1001/jama.2020.22196

Abd Aon MAA-K. Using HPRT gene mutation assay for detection of reasons of thyroid disorders in patients at Al- Zuaaffaranya city. Iraqi J Biotechnol. 2017;16(3).

Mendoza-León MJ, Mangalam AK, Regaldiz A, González- Madrid E, Rangel-Ramírez MA, Álvarez-Mardonez O, et al. Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases. Front Endocrinol (Lausanne). 2023;14:1192216. doi: 10.3389/fendo.2023.1192216. DOI: https://doi.org/10.3389/fendo.2023.1192216

Ludgate ME, Masetti G, Soares P. The relationship between the gut microbiota and thyroid disorders. Nat Rev Endocrinol. 2024 Sep;20(9):511–525. doi: 10.1038/s41574- 024-01003-w. DOI: https://doi.org/10.1038/s41574-024-01003-w

Milo T, Korem Kohanim Y, Toledano Y, Alon U. Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance. Trends Immunol. 2023;44(5):365–371. doi: 10.1016/j.it.2023.03.007. DOI: https://doi.org/10.1016/j.it.2023.03.007

Mohamad Fawzi S, Abdulhassan I, Mahdi B. Correlation between thyroid hormones and anti-TSHR Ab in graves’ disease Introduction. Iraqi J Biotechnol. 2018;17(1):60–66.

Zamwar UM, Muneshwar KN. Epidemiology, types, causes, clinical presentation, diagnosis, and treatment of hypothyroidism. Cureus. 2023;15 (9):e46241. doi: 10.7759/cureus.46241 DOI: https://doi.org/10.7759/cureus.46241

Mohammed S, Al-Jumaily E, Al-Hilal M. Evolution of Thyroid Autoantibodies and Thyroid Parameters in Iraqi Hypothyroidism Patients. Iraqi J Biotechnol. 2022;172–177.

Van Uytfanghe K, Ehrenkranz J, Halsall D, Hoff K, Loh TP, Spencer CA, et al. Thyroid stimulating hormone and thyroid hormones (triiodothyronine and thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status. Thyroid. 2023;33(9):1013– 1028. doi: 10.1089/thy.2023.0604. DOI: https://doi.org/10.1089/thy.2023.0169

Shulhai A-M, Rotondo R, Petraroli M, Patianna V, Predieri B, Iughetti L, et al. The role of nutrition on thyroid function. Nutrients. 2024;16(15):2496. doi: 10.3390/nu16152496. DOI: https://doi.org/10.3390/nu16152496

Lisco G, De Tullio A, Triggiani D, Zupo R, Giagulli VA, De Pergola G, et al. Iodine deficiency and iodine prophylaxis: An overview and update. Nutrients. 2023;15(4):1004. doi: 10.3390/nu15041004. DOI: https://doi.org/10.3390/nu15041004

Hasan Al-Saadi B, Jasim S. FOXO3 gene expression associated with oxidative stress in β-thalassemia Iraqi patients. Iraqi J Biotechnol. 2024;19(11). doi: 10.25303/1911rjbt1010107. DOI: https://doi.org/10.25303/1911rjbt1010107

Tan G, Zheng G, Li J, Zhu Y, Liang Z, Li H, et al. Association of genetic variations in FoxP3 gene with Graves’ disease in a Southwest Chinese Han population. Immun, Inflamm Dis. 2023;11(10):e1046. doi: 10.1002/iid3.1046. DOI: https://doi.org/10.1002/iid3.1046

Hasan Al-Saadi B. Polymorphism of FOXO3a gene and its association with incidence of asthma in Iraqi patients. Iraqi J Biotechnol. 2019;17(3):67–77.

Golzari-Sorkheh M, Zúñiga-Pflücker JC. Development and function of FOXP3+ regulators of immune responses. Clin Exp Immunol. 2023;213(1):13–22. doi: 10.1093/cei/uxad048. DOI: https://doi.org/10.1093/cei/uxad048

Goodi GAK, AL-Saadi BQ. Polymorphism of FOXO3a Gene and its association with incidence of asthma in Iraqi Patients. Iraqi J Biotechnol. 2018;17(3).

Borna S, Meffre E, Bacchetta R. FOXP3 deficiency, from the mechanisms of the disease to curative strategies. Immunol Rev. 2024;322(1):244–258. doi: 10.1111/imr.13289. DOI: https://doi.org/10.1111/imr.13289

Yaylacıoğlu Tuncay F, Serbest Ceylanoğlu K, Güntekin Ergün S, Ergün G, Konuk O. The role of FOXP3 polymorphisms in Graves’ disease with or without ophthalmopathy in a Turkish population. Turkish J Ophthalmol. 2024;54(2):69–75. doi: 10.4274/tjo.galenos.2024.37897. DOI: https://doi.org/10.4274/tjo.galenos.2024.37897

Shehjar F, Afroze D, Misgar RA, Malik SA, Laway BA. Association of FoxP3 promoter polymorphisms with the risk of Graves’ disease in ethnic Kashmiri population. Gene. 2018;672:88–92. doi: 10.1016/j.gene.2018.06.023. DOI: https://doi.org/10.1016/j.gene.2018.06.023

Zhang Y, Zhang J, Liu H, He F, Chen A, Yang H, et al. Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility. Medicine (Baltimore). 2019;98(38):e17224. doi: 10.1097/md.0000000000017224. DOI: https://doi.org/10.1097/MD.0000000000017224

Mohammed MQ, Alwan AH, Almukhtar AA. Estimation of serum TLR-9, TNF-α, and IL-6 levels in the Iraqi patients diagnosed as acute myelogenous leukemia. Baghdad Sci J. 2023;21(7):2182–2190. doi: 10.21123/bsj.2023.9056. DOI: https://doi.org/10.21123/bsj.2023.9056

SPSS. Statistical Package for the Social Sciences. 2019. p. Version 26.

Qasim Mohammed M, Hussein Alwan A, Amer Almukhtar A, Kareem Aneed Al-Saedi M. Revealing of TLR-9 gene polymorphisms by qPCR HRM technique and their influence on TLR-9 serum level in acute myeloid leukemia patients: Case-control study. Cytokine. 2024;182:156730. doi: 10.1016/j.cyto.2024.156730. DOI: https://doi.org/10.1016/j.cyto.2024.156730

Fadhil M, Razaq S, Al-Kareem A, Al-Kazaz A. Study the association between IL-17 level and autoimmune antibodies in hypo and hyperthyroidism patients. Iraqi J Sci. 2019:60(9):1967-1976.‏ doi: 10.24996/ijs.2019.60.9.9. DOI: https://doi.org/10.24996/ijs.2019.60.9.9

Abed RM, Abdulmalek HW, Yaaqoob LA, Altaee MF, Kamona ZK. Serum level and genetic polymorphism of IL-38 and IL-40 in autoimmune thyroid disease. Iraqi J Sci. 2023:64(6):2786-2797.‏ doi: 10.24996/ijs.2023.64.6.12. DOI: https://doi.org/10.24996/ijs.2023.64.6.12

Yassin AH, Al-Kazaz AK., Rahmah AM, Ibrahim TY. Association of CTLA-4 single nucleotide polymorphisms with autoimmune hypothyroidism in Iraqi patients. Iraqi J Sci. 2022:63(7):2891-2899.‏ doi: 10.24996/ijs.2022.63.7.13. DOI: https://doi.org/10.24996/ijs.2022.63.7.13

Fröhlich E, Wahl R. Thyroid autoimmunity: Role of anti- thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521. doi: 10.3389/fimmu.2017.00521. DOI: https://doi.org/10.3389/fimmu.2017.00521

Rydzewska M, Jaromin M, Pasierowska IE, Stożek K, Bossowski A. Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases. Thyroid Res. 2018;11:2. doi: 10.1186/s13044-018-0046-9. DOI: https://doi.org/10.1186/s13044-018-0046-9

Bogusławska J, Godlewska M, Gajda E, Piekiełko- Witkowska A. Cellular and molecular basis of thyroid autoimmunity. Eur Thyroid J. 2022;11(1). doi: 10.1530/etj- 21-0024. DOI: https://doi.org/10.1530/ETJ-21-0024

Oparaugo NC, Ouyang K, Nguyen NPN, Nelson AM, Agak GW. Human regulatory T cells: Understanding the role of Tregs in select autoimmune skin diseases and post- transplant nonmelanoma skin cancers. Int J Mol Sci. 2023;24(2). doi: 10.3390/ijms24021527. DOI: https://doi.org/10.3390/ijms24021527

Goswami TK, Singh M, Dhawan M, Mitra S, Bin ET, Rabaan AA, et al. Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders- Advances and challenges. Hum Vaccin Immunother. 2022;18(1):2035117. doi: 10.1080/21645515.2022.2035117. DOI: https://doi.org/10.1080/21645515.2022.2035117

Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011;241(1):260–268. doi: 10.1111/j.1600-065x.2011.01018.x. DOI: https://doi.org/10.1111/j.1600-065X.2011.01018.x

Fakour P, Shirizadeh A, Tahamoli-Roudsari A, Solgi G. Epigenetic regulation of FOXP3 gene expression in relation to impaired function of regulatory T cells in systemic lupus erythematosus. Explor Immunol. 2024;4(5):640–657. doi: 10.37349/ei.2024.00164. DOI: https://doi.org/10.37349/ei.2024.00164

Akber NT, Yenzeel JH. Evaluation of some biochemical parameters in Iraqi patients with hyperthyroidism. Iraqi J Biotechnol. 2023;22(1).

Paradowska-Gorycka A, Jurkowska M, Felis-Giemza A, Romanowska-Próchnicka K, Manczak M, Maslinski S, et al. Genetic polymorphisms of Foxp3 in patients with rheumatoid arthritis. J Rheumatol. 2015;42(2):170–180. doi: 10.3899/jrheum.131381. DOI: https://doi.org/10.3899/jrheum.131381

Ikram EM, Allam AA, Meawed TE, Abd El-Wahab SM, Ramadan RA. Forkhead Box P3 (Foxp3) serum level and Foxp3 Gene-Promoter polymorphisms in Egyptian rheumatoid arthritis patients: A case-control study. Egypt J Immunol. 2021;28(2):53–64. DOI: https://doi.org/10.55133/eji.280206

Ssedyabane F, Niyonzima N, Ngonzi J, Nambi Najjuma J, Mudondo H, Okeny C, et al. FOXP3 serum concentration; a likely predictor of CIN and cervical cancer: Secondary analysis from a case-control study at a clinic in Southwestern Uganda. Gynecol Oncol Rep. 2024;55:101466. doi: 10.1016/j.gore.2024.101466 DOI: https://doi.org/10.1016/j.gore.2024.101466

Widaningsih Y, Natsir R, Arif M, Bahrun U, Kasim H, Kadir NA, et al. Foxp3 serum levels in contrast-induced nephropathy patients after the administration of contrast media. Int J Biomed Mater Res. 2017;5(2):25–28. doi: 10.11648/j.ijbmr.20170502.12. DOI: https://doi.org/10.11648/j.ijbmr.20170502.12

Li HN, Li XR, Du YY, Yang ZF, Lv ZT. The association between Foxp3 polymorphisms and risk of Graves’ disease: A systematic review and meta-analysis of observational studies. Front Endocrinol (Lausanne). 2020;11:392. doi: 10.3389/fendo.2020.00392 DOI: https://doi.org/10.3389/fendo.2020.00392

Bossowski A, Borysewicz-Sańczyk H, Wawrusiewicz- Kurylonek N, Zasim A, Szalecki M, Wikiera B, et al. Analysis of chosen polymorphisms in FoxP3 gene in children and adolescents with autoimmune thyroid diseases. Autoimmunity. 2014;47(6):395–400. doi: 10.3109/08916934.2014.910767. DOI: https://doi.org/10.3109/08916934.2014.910767

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Published

2025-03-16

How to Cite

Muayad, B. A., & Jassim, H. A. (2025). Role of FOXP3 (rs3761548) Polymorphism in Modulating FOXP3 Protein Level in Iraqi Patients with Thyroid Disorder . Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 8(1), 208–214. https://doi.org/10.54133/ajms.v8i1.1684

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