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Predisposition to Graves' Disease and Graves' Ophthalmopathy by Genetic Variants of IL2RA
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  • Juan Du,
  • Xin Wang,
  • Guiqin Tan,
  • Wenwen Wei,
  • Fangyu Zhou,
  • Zhongzhi Liang,
  • Hua Li,
  • Hongsong Yu
Juan Du
Zunyi Medical University
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Xin Wang
Zunyi Medical University
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Guiqin Tan
Zunyi Medical University
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Wenwen Wei
Zunyi Medical University
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Fangyu Zhou
Zunyi Medical University
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Zhongzhi Liang
Zunyi Medical University
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Hua Li
Chongqing Medical University
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Hongsong Yu
Zunyi Medical University
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Abstract

Previous studies have identified that Th17/Treg cells were involved in Graves’ disease (GD). This study aimed at clarifying the association between GD susceptibility and single nucleotide polymorphisms (SNPs) of Th17/Treg cells-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. The result demonstrated that significantly increased frequencies of IL2RA/rs3118470 TT genotype (Pc=2.212×10-3) and IL2RA/rs2104286 AA genotype (Pc=1.754×10-5) were observed in GD. Stratification analysis also revealed that rs3118470 TT genotype and rs2104286 AA genotype were associated with Graves’ ophthalmopathy (GO) susceptibility (Pc = 1.848×10-6, Pc = 1.230×10-3, respectively). 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 carriers with the rs3118470 risk genotype had decreased anti-inflammatory cytokine levels (IL-10 and TGF-β1) and increased IL-17 secretion than protective genotype individuals (P < 0.05). For the rs2104286 locus, 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/ (rs3118470, rs2104286) were associated with GD and GO susceptibility in Southwest Chinese Han population.