Analysis of Polymorphisms rs7093069-IL-2RA, rs7138803-FAIM2, and rs1748033-PADI4 in the Group of Adolescents With Autoimmune Thyroid Diseases

Sawicka, Beata; Borysewicz-Sańczyk, Hanna; Wawrusiewicz‐Kurylonek, Natalia; Aversa, Tommaso; Corica, Domenico; Gościk, Joanna; Krętowski, Adam; Waśniewska, Małgorzata; Bossowski, Artur

doi:10.3389/fendo.2020.544658

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…This result was of particular interest, because it showed that GD and GO shared a common genetic susceptibility locus, which needs to be further investigated in view of the fact that both diseases are different in pathogenesis. Previous studies found that IL2RA/rs7093069 was significantly associated with susceptibility to GD in Caucasian [40,41], while the results of our study showed that IL2RA/rs7093069 was not significantly associated with GD susceptibility in Southwest China. The reason for the inconsistent results may be due to different genetic background of people in different regions and the sample size involved in the study.…”

Section: Discussioncontrasting

confidence: 94%

Predisposition to Graves’ disease and Graves’ ophthalmopathy by genetic variants of IL2RA

Wang

Tan

et al. 2021

J Mol Med

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Previous studies have identified that Th17/Treg cells were involved in the occurrence and development of Graves' disease (GD). This study aimed at clarifying the association between GD susceptibility and nine single nucleotide polymorphisms (SNPs) of Th17/Treg cell-related genes, including IL2RA, miR27a, miR182, and FoxO1. A two-stage association study was performed in 650 GD patients and 1300 healthy controls. PCR-RFLP assays, real-time PCR, and ELISA were performed. In the first stage, association analysis has identified that IL2RA/rs3118470 TT genotype (Pc = 0.027, OR = 1.688) and IL2RA/rs2104286 AA genotype (Pc = 0.027, OR = 1.658) has significantly increased frequencies in patients with GD than control subjects. In the second stage, the result of rs2104286 was consistent with the first-stage results (AA genotype: Pc = 0.006, OR = 1.618). The combined data showed that IL2RA/rs2104286 AA genotype had increased frequencies in patients with GD (Pc = 8.772 × 10 −6 , OR = 1.636). Stratification analysis also revealed that rs2104286 AA genotype was significantly associated with Graves' ophthalmopathy (GO) susceptibility (Pc = 9.150 × 10 −4 , OR = 1.851). Functional studies showed that carriers of the rs2104286 AA genotype had lower IL2RA mRNA expression than AG genotype carriers (P = 0.021). Cytokine analyses revealed that the rs2104286 AA genotype individuals had lower IL-10 levels (P = 0.015) and increased IL-17 levels than AG genotype carriers (P = 1.467 × 10 −4 ). In conclusion, our findings suggested that IL2RA/rs2104286 was associated with GD and GO susceptibility in Southwest Chinese Han population, which may be involved in the occurrence of GD and GO by affecting the mRNA expression of IL2RA gene and the cytokine production. Key messages• We identified that IL2RA/rs2104286 locus contributed to the predisposition of Graves' disease (GD) and Graves' ophthalmopathy (GO). • Functional analyses suggested that IL2RA/rs2104286 may participate in the occurrence of GD and GO by affecting the mRNA expression of IL2RA and cytokine (IL-10 and IL-17) secretion. • We found that IL2RA (rs3118470, rs7093069), miR27a/ rs895819, miR182/rs76481776, and FoxO1 (rs2297626, rs17592236, rs9549241, rs12585277) loci polymorphisms were not associated with GD susceptibility.

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Section: Discussioncontrasting

confidence: 94%

Predisposition to Graves’ disease and Graves’ ophthalmopathy by genetic variants of IL2RA

Wang

Tan

et al. 2021

J Mol Med

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“…Genetic predisposition and environmental factors contribute to the development of autoimmune thyroid disease. Polymorphism of genes occurs in genetically predisposed individuals [ 13 ]. Deficiency in suppressor T cells and loss of self-tolerance are mainly involved in the pathogenesis of GD [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with graves’ disease

Man

Sun

et al. 2021

Ital J Pediatr

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Background Glucocorticoid treatment is used in children with Graves’ disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p < 0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). Conclusions The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

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“…CTLA4, IL-2RA and PTPN22) and thyroid-specific genes (e.g. TG and TSHR) (13,14,15). HCP5 polymorphisms have been associated with a younger age at GD onset (16,17).…”

Section: Definitive Treatment In Pediatric Gd -Radioiodine (Rai)mentioning

confidence: 99%

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

Mooij

Cheetham

Verburg

et al. 2022

European Thyroid Journal

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Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

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Analysis of Polymorphisms rs7093069-IL-2RA, rs7138803-FAIM2, and rs1748033-PADI4 in the Group of Adolescents With Autoimmune Thyroid Diseases

Cited by 14 publications

References 31 publications

Predisposition to Graves’ disease and Graves’ ophthalmopathy by genetic variants of IL2RA

Predisposition to Graves’ disease and Graves’ ophthalmopathy by genetic variants of IL2RA

Effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with graves’ disease

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

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