Association Between FOXP3 rs2232368 Variant and Hashimoto's Thyroiditis Risk: A Case-Control Study

Sarah Kassab Shandaway Al-Zamali; Iman Mohammad Said Jallod; Shahad Saad Mohammed; Mohammed Sameir

doi:10.7759/cureus.79126

Association Between FOXP3 rs2232368 Variant and Hashimoto's Thyroiditis Risk: A Case-Control Study

Cureus. 2025 Feb 16;17(2):e79126. doi: 10.7759/cureus.79126. eCollection 2025 Feb.

Authors

Sarah Kassab Shandaway Al-Zamali¹, Iman Mohammad Said Jallod², Shahad Saad Mohammed³, Mohammed Sameir⁴

Affiliations

¹ Medical Microbiology, Hammurabi College of Medicine, University of Babylon, Hillah, IRQ.
² Basic Science Nursing, College of Nursing, University of Telafer, Telafer, IRQ.
³ Public Health Sciences, Technical Institute of Babylon, Al-Furat Al-Awsat Technical University, Najaf, IRQ.
⁴ Clinical Autoimmune Therapy, Hammurabi College of Medicine, University of Babylon, Hillah, IRQ.

Abstract

Background and aim Hashimoto's thyroiditis (HT) pathogenesis is characterized by a dysregulation of immune tolerance, which may be influenced by genetic variations in the FOXP3 gene, a key regulator of T-regulatory cell function. However, the role of specific FOXP3 polymorphisms in HT susceptibility is not yet fully understood, particularly in Middle Eastern populations. This study aims to explore the association between the FOXP3 rs2232368 polymorphism and HT susceptibility in an Iraqi population while also examining its relationship with thyroid function parameters. Methods This case-control study included 60 HT patients and 40 healthy controls from the Medical City Educational Laboratories in Baghdad (October 2022 to September 2023). HT diagnosis was based on established clinical and laboratory criteria. Thyroid function (thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4)) was measured using the mini VIDAS^® system (bioMérieux, Craponne, France). FOXP3 rs2232368 genotyping was performed using ARMS-PCR. Genetic associations were assessed through ORs with 95% CIs, adjusting for demographic and clinical variables. Results HT patients exhibited significant thyroid dysfunction compared to controls (median TSH: 18.82 vs. 2.66 mIU/L, p < 0.001; T3: 0.53 vs. 2.33 nmol/L, p < 0.001; T4: 8.12 vs. 43.5 μg/dL, p < 0.001). The AA genotype was associated with a significantly increased risk of HT (OR = 4.66, 95% CI: 1.32-16.44, p = 0.017), while the heterozygous GA genotype showed a nonsignificant trend (OR = 2.28, 95% CI: 0.84-6.19, p = 0.108). The A allele was strongly associated with HT susceptibility (OR = 2.98, 95% CI: 1.54-5.77, p = 0.001). These associations remained significant after adjusting for BMI and thyroid parameters. Conclusions This study identifies FOXP3 rs2232368 as a significant genetic risk factor for HT in the Iraqi population, with the AA genotype associated with nearly a five-fold increased susceptibility. These findings enhance our understanding of the genetic basis of HT and may inform risk stratification strategies for Middle Eastern populations. Further research is needed to explore the functional implications of this polymorphism in thyroid autoimmunity.

Keywords: autoimmune disorder; foxp3 gene; hashimoto's thyroiditis; regulatory t cell; rs2232368 polymorphism.