The MAGI2 gene polymorphism rs2160322 is associated with Graves' disease but not with Hashimoto's thyroiditis

J Endocrinol Invest. 2019 Jul;42(7):843-850. doi: 10.1007/s40618-018-0990-1. Epub 2018 Dec 8.


Purpose: Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune disorders, predominantly including Graves' disease (GD), and Hashimoto's thyroiditis (HT). This study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in MAGI2 and MAGI3 gene contributed to the etiology of AITDs.

Methods: We conducted a case-control study including 1001 patients with AITDs (625 GD, 376 HT) and 846 healthy controls. Subgroup analyses in GD and HT were also performed.

Results: The genotypes of rs2160322 in MAGI2 showed a borderline association with AITDs (P = 0.048), and they had a strong correlation with GD (P = 0.012). The frequency of the minor allele G of rs2160322 was significantly higher in the GD patients than in the controls (P = 0.027; OR 1.91; 95% CI 1.020-1.391), especially for GD females (P = 0.008; OR 1.304; 95% CI 1.072-1.587), and those who had positive family history (P = 0.011; OR 1.412; 95% CI 1.083-1.843). For genetic model analysis, the recessive model and homozygous model of rs2160322 showed significant associations with AITDs (P = 0.009; P = 0.019) and GD (P = 0.004; P = 0.005). Nevertheless, our study could not identify any relationship between these SNPs and HT. Due to the low mutation rate of rs1343126 in MAGI3, we were unable to obtain a credible conclusion on its association with AITDs.

Conclusions: Our study identified that MAGI2 rs2160322 was strongly associated with GD susceptibility. The potential dysfunction of tight junction proteins and aberrant epithelial barrier caused by abnormal MAGI2 expression may be a novel mechanism of GD.

Keywords: Autoimmune thyroid diseases; Graves’ disease; Hashimoto’s thyroiditis; MAGI2; Single-nucleotide polymorphisms.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Biomarkers / analysis*
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Graves Disease / genetics*
  • Graves Disease / pathology*
  • Guanylate Kinases
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / pathology*
  • Humans
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prognosis


  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Carrier Proteins
  • Guanylate Kinases
  • MAGI2 protein, human