Predisposition to Graves' Disease and Graves' Ophthalmopathy by Genetic
Variants of IL2RA
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.