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

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

Sarah Kassab Shandaway Al-Zamali  1 , Iman Mohammad Said Jallod  2 , Shahad Saad Mohammed  3 , Mohammed Sameir  4
Affiliations

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

Sarah Kassab Shandaway Al-Zamali et al. Cureus. .

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.

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Conflict of interest statement

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Public Health Directorate/Ministry of Health/Republic of Iraq issued approval 2021/04/25-411. This study was approved by the Public Health Directorate/Ministry of Health/Republic of Iraq, and informed consent was obtained from all participants prior to sample collection. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Serum TSH levels in patients with HT compared to healthy controls
S = significance at p < 0.05 HT, Hashimoto’s thyroiditis; TSH, thyroid-stimulating hormone
Figure 2
Figure 2. Serum T4 levels in patients with HT compared to healthy controls
S = significance at p < 0.05 HT, Hashimoto’s thyroiditis; T4, thyroxine
Figure 3
Figure 3. Serum T3 levels in patients with HT compared to healthy controls
S = significance at p < 0.05 HT, Hashimoto’s thyroiditis; T3, triiodothyronine
Figure 4
Figure 4. Agarose gel electrophoresis of ARMS-PCR products for FOXP3 rs2232368 (G/A) gene polymorphism in patients
Wild-type homozygotes (GG) show amplification of the G allele only, while mutant homozygotes (AA) display amplification of the A allele only. Heterozygotes (GA) exhibit both G and A alleles. Marker (M) range: 2,000-100 bp ARMS-PCR, Amplification Refractory Mutation System PCR
See this image and copyright information in PMC

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