The International Journal of Romanian Society of Endocrinology / Registered in 1938

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Acta Endocrinologica(Bucharest) is live in PubMed Central

October - December 2019, Volume 15, Issue 4
General Endocrinology

Kalantar K, Khansalar S, Eshkevar Vakili M, Ghasemi D, Dabbaghmanesh MH, Amirghofran Z

Association of FOXP3 Gene Variants with Risk Of Hashimoto’s Thyroiditis and Correlation with Anti-TPO Antibody Levels

Acta Endo (Buc) 2019, 15 (4): 423-429
doi: 10.4183/aeb.2019.423

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Keywords: Hashimoto’s thyroiditis, Regulatory T cell, Foxp3 gene, polymorphism.

Correspondence: Zahra Amirghofran MD, Shiraz University of Medical Sciences, School of Medicine, Department of Immunology, Zand st. Shiraz, 7134845794, Iran, E-mail: