Polymorphic Variants of FOXP3 Gene (rs 3761548) and (rs 3761549) are Significantly Associated with the Risk for Recurrent Pregnancy Losses. A Study in High Incidence Zone (Kashmir, North India)
References
- Dimitriadis E, Menkhorst E, Saito S, Kutteh WH, Brosens JJ. Recurrent pregnancy loss. Nat Rev Dis Primers. 2020 Dec 10;6(1):98. doi: 10.1038/s41572-020-00228-z.
- Hong Li Y, Marren A. Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice. Aust J Gen Pract. 2018 Jul;47(7):432–6. doi: 10.31128/AJGP-01-18-4459.
- Almawi WY, Al-Shaikh FS, Melemedjian OK, Almawi AW. Protein Z, an anticoagulant protein with expanding role in reproductive biology. Reproduction. 2013 Jun 27;146(2):R73–80. doi: 10.1530/REP-13-0072.
- Manzoor U, Pandith AA, Amin I, Wani S, Sanadhya D, Lone TA, et al. Implications of decreased expression of mir-125a with respect to its variant allele in the pathogenesis of recurrent pregnancy loss: A study in a high incidence zone. J Clin Med. 2022 Jul 1;11(13):3834. doi: 10.3390/jcm11133834.
- Manzoor U, Pandith AA, Amin I, Wani S, Baba SM, Wani UM, et al. Regulatory role of miR-125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses. Int J Gynaecol Obstet. 2024 Sep;166(3):1285–96. doi: 10.1002/ijgo.15496.
- Wilczyński JR. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism? Hum Immunol. 2006 Jul;67(7):492–511. doi: 10.1016/j.humimm.2006.04.007.
- Zenclussen AC, Gerlof K, Zenclussen ML, Ritschel S, Zambon Bertoja A, Fest S, et al. Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface. Eur J Immunol. 2006 Jan;36(1):82–94. doi: 10.1002/eji.200535428.
- Mei S, Tan J, Chen H, Chen Y, Zhang J. Changes of CD4+CD25 high regulatory T cells and FOXP3 expression in unexplained recurrent spontaneous abortion patients. Fertil Steril. 2010 Nov;94(6):2244–7. doi: 10.1016/j.fertnstert.2009.11.020.
- Coffer PJ, Burgering BM. Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol. 2004 Nov;4(11):889–99. doi: 10.1038/nri1488.
- Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006 Jul 28;126(2):375–87. doi: 10.1016/j.cell.2006.05.042.
- Inoue N, Watanabe M, Morita M, Tomizawa R, Akamizu T, Tatsumi K, et al. Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases. Clin Exp Immunol. 2010 Dec;162(3):402–6. doi: 10.1111/j.1365-2249.2010.04229.x.
- Bassuny WM, Ihara K, Sasaki Y, Kuromaru R, Kohno H, Matsuura N, et al. A functional polymorphism in the promoter/enhancer region of the FOXP3/Scurfin gene associated with type 1 diabetes. Immunogenetics. 2003 Jun;55(3):149–156. doi: 10.1007/s00251-003-0559-8.
- Naderi-Mahabadi F, Zarei S, Fatemi R, Kamali K, Pahlavanzadeh Z, Jeddi-Tehrani M, et al. Association study of forkhead box P3 gene polymorphisms with unexplained recurrent spontaneous abortion. J Reprod Immunol. 2015 Aug;110:48–53. doi: 10.1016/j.jri.2015.04.001.
- Saxena D, Misra MK, Parveen F, Phadke SR, Agrawal S. The transcription factor Forkhead Box P3 gene variants affect idiopathic recurrent pregnancy loss. Placenta. 2015 Feb;36(2):226–31. doi: 10.1016/j.placenta.2014.11.014.
- Fan MY, Turka LA. Immunometabolism and PI(3)K signaling as a link between IL-2, Foxp3 expression, and suppressor function in regulatory T cells. Front Immunol. 2018 Jan 29;9:69. doi: 10.3389/fimmu.2018.00069.
- Jenkins C, Roberts J, Wilson R, MacLean MA, Shilito J, Walker JJ. Evidence of a T(H) 1 type response associated with recurrent miscarriage. Fertil Steril. 2000 Jun;73(6):1206–8. doi: 10.1016/s0015-0282(00)00517-3.
- Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. 2000 Mar;15(3):713–8. doi: 10.1093/humrep/15.3.713.
- Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol. 2007 Mar;8(3):277–84. doi: 10.1038/ni1437. Epub 2007 Jan 14.
- Jaber MO, Sharif FA. Association between functional polymorphisms of Foxp3 and Interleukin-21 genes with the occurrence of recurrent pregnancy loss in Gaza strip-Palestine. Int J Res Med Sci. 2014 Oct–Dec;2(4):1687–93. Available from:
https://www.msjonline.org/index.php/ijrms/article/view/2486 . Published online 2017 Jan 26. - Wu Z, You Z, Zhang C, Li Z, Su X, Zhang X, Li Y. Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population. Clin Dev Immunol. 2012;2012:896458. doi: 10.1155/2012/896458. Epub 2011 Jul 13.
- Sharif FA, Ashour MJ, Badawi NT, Al-Ashi SF. Polymorphism in regulatory T-cell (Treg)-related genes is associated with unexplained recurrent pregnancy loss. american journal of clinical and experimental medicine. 2016 May 11;4(3):63–7. doi: 10.11648/j.ajcem.20160403.15.
- Dirsipam K, Ponnala D, Madduru D, Bonu R, Jahan P. Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study. Am J Reprod Immunol. 2021 Sep;86(3):e13431. doi: 10.1111/aji.13431. Epub 2021 May 10.
- Bamba C, Rohilla M, Kumari A, Kaur A, Srivastava P. Influence of forkhead box protein 3 gene polymorphisms in recurrent pregnancy loss: A meta-analysis. Placenta. 2024 Feb;146:79–88. doi: 10.1016/j.placenta.2024.01.003. Epub 2024 Jan 4.
- Hadinedoushan H, Abbasirad N, Aflatoonian A, Eslami G. The serum level of transforming growth factor beta1 and its association with Foxp3 gene polymorphism in Iranian women with recurrent spontaneous abortion. Hum Fertil (Camb). 2015 Mar;18(1):54–9. doi: 10.3109/14647273.2014.927594. Epub 2014 Jul 14.
- Mishra S, Srivastava A, Mandal K, Phadke SR. Study of the association of forkhead box P3 (FOXP3) gene polymorphisms with unexplained recurrent spontaneous abortions in Indian population. J Genet. 2018 Jun;97(2):405–10. doi: 10.1007/s12041-018-0917-9.
- Ghasemi Z, Kalantar K, Amirghofran Z. The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy. Mol Biol Rep. 2021 Feb;48(2):1139–50. doi: 10.1007/s11033-021-06154-x. Epub 2021 Jan 30.
- Fazelzadeh Haghighi M, Ali Ghayumi M, Behzadnia F, Erfani N. Investigation of FOXP3 genetic variations at positions −2383 C/T and IVS9+459 T/C in southern Iranian patients with lung carcinoma. Iran J Basic Med Sci. 2015 May;18(5):465–71. doi: 10.22038/ijbms.2015.4408.
- Song QH, Shen Z, Xing XJ, Yin R, Wu YZ, You Y, et al. An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris. Indian J Biochem Biophys. 2012 Feb;49(1):25–35. Available at:
https://nopr.niscpr.res.in/handle/123456789/13588 . - Lan Y, Tang XS, Qin J, Wu J, Qin JM. [Association of transcription factor FOXP3 gene polymorphism with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. Chinese J of Med Gen. 2010 Aug;27(4):433–6. Chinese. doi: 10.3760/cma.j.issn.1003-9406.2010.04.016.
- André GM, Barbosa CP, Teles JS, Vilarino FL, Christofolini DM, Bianco B. Analysis of FOXP3 polymorphisms in infertile women with and without endometriosis. Fertil Steril. 2011 Jun;95(7):2223–7. doi: 10.1016/j.fertnstert.2011.03.033. Epub 2011 Apr 9.
- Tian T, Wang M, Zheng Y, Yang T, Zhu W, Li H, et al. Association of two FOXP3 polymorphisms with breast cancer susceptibility in Chinese Han women. Cancer Manag Res. 2018 Apr 26;10:867–872. doi: 10.2147/CMAR.S158433.
DOI: https://doi.org/10.34763/jmotherandchild.20252901.d-25-00030 | Journal eISSN: 2719-535X | Journal ISSN: 2719-6488
Language: English
Page range: 219 - 226
Submitted on: Aug 11, 2025
Accepted on: Sep 12, 2025
Published on: Dec 4, 2025
Published by: Institute of Mother and Child
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year
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© 2025 Usma Manzoor, Arshad A. Pandith, Tawseef A. Lone, Amreena Hameed, Falak U Nisa, Ina Amin, Shayesta Rah, Saima Wani, Shayaq Ul Abeer Rasool, Adil Lateef, Aabida Ahmad, published by Institute of Mother and Child
This work is licensed under the Creative Commons Attribution 4.0 License.