loading page

Predisposition to Graves' Disease and Graves' Ophthalmopathy by Genetic Variants of IL2RA
  • +5
  • Juan Du,
  • Xin Wang,
  • Guiqin Tan,
  • Wenwen Wei,
  • Fangyu Zhou,
  • Zhongzhi Liang,
  • Hua Li,
  • Hongsong Yu
Juan Du
Zunyi Medical University

Corresponding Author:[email protected]

Author Profile
Xin Wang
Zunyi Medical University
Author Profile
Guiqin Tan
Zunyi Medical University
Author Profile
Wenwen Wei
Zunyi Medical University
Author Profile
Fangyu Zhou
Zunyi Medical University
Author Profile
Zhongzhi Liang
Zunyi Medical University
Author Profile
Hua Li
Chongqing Medical University
Author Profile
Hongsong Yu
Zunyi Medical University
Author Profile

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.
Oct 2021Published in Journal of Molecular Medicine volume 99 issue 10 on pages 1487-1495. 10.1007/s00109-021-02111-0