Polymorphisms of the TNFAIP3 region and Graves' disease

Autoimmunity. 2014 Nov;47(7):459-65. doi: 10.3109/08916934.2014.914504. Epub 2014 May 6.


Autoimmune thyroid disease (AITD) is a multifactorial organ-specific autoimmune disorder, and both genetic susceptibility and environmental factors are involved in its etiology. TNFAIP3 encodes the ubiquitin-modifying enzyme (A20), a key regulator of inflammatory signaling pathways. The aim of the present study was to evaluate the association between TNFAIP3 gene polymorphisms and AITD in Chinese Han population. Three single nucleotide polymorphisms (SNPs) in TNFAIP3 gene locus (rs598493, rs610604 and rs661561) were detected in a set of 667 patients with AITD and 301 controls in Han Chinese population using the Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform. Compared with those of the controls, the frequencies of GG genotype of rs598493, the AA genotype of rs610604, the allele G and GG genotype of rs661561 were significantly increased in Graves' disease (GD) patients. However, the frequencies of AG genotype of rs598493 and AC genotype of rs610604 were significantly decreased in GD patients. The ATC haplotype (rs598493, rs661561 and rs610604) was associated with a decreased risk of GD. No significant differences in the three SNPs were observed between HT patients and controls. Our study shows a clear association between the polymorphisms of TNFAIP3 gene and GD, not HT, suggesting that TNFAIP3 gene is likely to be a genetic susceptibility factor to GD.

Keywords: Autoimmune thyroid disease; Graves'; Hashimoto's thyroiditis; disease; single nucleotide polymorphism; tumor necrosis factor α-induced protein 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asians
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Graves Disease / genetics*
  • Hashimoto Disease / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Tumor Necrosis Factor alpha-Induced Protein 3


  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3