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TP53 密码子 72 多态性与 1 型糖尿病患者并发症和合并症的关系。

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes.

机构信息

Department of Medical Immunology, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 1, 80-211, Gdańsk, Poland.

Chair & Clinics of Paediatrics, Diabetology and Endocrinology, Faculty of Medicine, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland.

出版信息

J Mol Med (Berl). 2021 May;99(5):675-683. doi: 10.1007/s00109-020-02035-1. Epub 2021 Jan 25.

Abstract

Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. KEY MESSAGES: We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

摘要

野生型 TP53 在调节免疫反应和全身炎症中发挥重要作用。在 1 型糖尿病 (T1D) 中,TP53 途径上调,观察到细胞凋亡的易感性增加。我们假设 TP53 密码子 72 多态性与 T1D 患者的并发症和合并症有关。我们研究了 TP53 密码子 72 多态性与 T1D 并发症和合并症(视网膜病变、肾病、高血压、血脂异常、自身免疫性甲状腺炎和乳糜泻)的关系在 350 名患者中。我们方法的主要结果如下:(1)在糖尿病患者中,Pro/Pro 基因型与微血管并发症、血脂异常和乳糜泻的风险增加有关;(2)Arg/Arg 变体与自身免疫性甲状腺炎和乳糜泻的风险降低有关;(3)Pro 等位基因与血脂异常、自身免疫性甲状腺炎和乳糜泻的风险增加有关。尽管还需要进一步的研究,但我们的结果首次表明,TP53 密码子 72 多态性可以被认为是预测某些 T1D 并发症和合并症易感性的遗传标志物。关键信息:我们分析了 T1D 患者的 TP53 密码子 72 多态性。Pro/Pro 基因型与微血管并发症、血脂异常和乳糜泻的风险增加有关。Arg/Arg 变体与自身免疫性甲状腺炎和乳糜泻的风险降低有关。Pro 等位基因与血脂异常、自身免疫性甲状腺炎和乳糜泻的风险增加有关。

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