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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) Cover

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)

Open Access
|Dec 2025

Abstract

Objective

Recurrent Pregnancy Loss (RPL) is a significant pregnancy complication with a multifactorial aetiology and is a vital reproductive health concern that globally affects 2–5% of women. Polymorphic gene variation causes alteration in FOXP3 gene that impairs the Treg cells which leads to complications in pregnancy outcome. Thus, we aimed to study an association between FOXP3 polymorphic variations (rs3761548 and rs3761549) and RPL.

Material and methods

This case control study comprised of 120 RPL cases and 150 healthy multiparous women as control group with at least one full term pregnancy and no history of pregnancy loss matched to cases according to age and geographic origins. Genotyping for FOXP3 was analyzed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP).

Results

Significantly higher frequency of FOXP3 −3279 C/A (rs 3761548)heterozygous AC and homozygous AA was found in RPL cases than controls (63.3% vs. 46%, O.R = 2.53): p = 0.0006 and (11.7% vs. 8%; O.R 2.68): p = 0.03 respectively. Moreover, the dominant model (AC +AA) and allele A were seen implicated more in RPL cases vs. healthy control (75% vs. 54%; O.R = 2.5): p = 0.0005 and (43.3% vs. 31%; O.R = 1.7): p = 0.003. For FOXP3 −2383 C/T (rs 3761548), homozygous genotype TT was significantly higher in RPL cases than the control group against the wild type CC genotype with O. R= 3.49 (p = 0.04). Further, FOXP3 (rs 3761548) genotypes AC+AA were significantly associated between cases and control in terms of women without any known family history (p = 0.0009) and consanguinity (p = 0.0002), respectively.

Conclusion

The study concludes that both the variants of FOXP3 gene, C/A (−3279) and C/T (−2383) are significantly associated with an increased risk for recurrent pregnancy losses.

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

© 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.