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

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.

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.

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.

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.