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

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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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Acknowledgements

The present work was supported by grants from the National Natural Science Foundation of China (nos. 81670722 and 81471004).

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Authors and Affiliations

  1. Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai, 201508, China

    X. Jia, B. Wang & J. Zhang

  2. Department of Endocrinology and Metabolism, Zhongshan Hospital of Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China

    T. Zhai

  3. Department of Emergency, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai, 201508, China

    F. Zhang

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  1. X. Jia
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  2. T. Zhai
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  3. B. Wang
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  4. J. Zhang
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  5. F. Zhang
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Correspondence to J. Zhang or F. Zhang.

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The authors declare that they have no conflict of interest.

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The experiment was approved by the ethics committee of Jinshan Hospital of Fudan University.

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Informed consent was signed in both the patient group and the control group. All subjects in this experiment were voluntary and did not receive any financial compensation.

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Jia, X., Zhai, T., Wang, B. et al. The MAGI2 gene polymorphism rs2160322 is associated with Graves’ disease but not with Hashimoto’s thyroiditis. J Endocrinol Invest 42, 843–850 (2019). https://doi.org/10.1007/s40618-018-0990-1

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  • DOI: https://doi.org/10.1007/s40618-018-0990-1

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