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  • Title: The MAGI2 gene polymorphism rs2160322 is associated with Graves' disease but not with Hashimoto's thyroiditis.
    Author: Jia X, Zhai T, Wang B, Zhang J, Zhang F.
    Journal: J Endocrinol Invest; 2019 Jul; 42(7):843-850. PubMed ID: 30535759.
    Abstract:
    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.
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