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 messagesWe 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.
Highlights
Wild-type TP53 has been established as a tumor suppressor in human cancer as it plays an important role in the control of cell proliferation and death
Key messages & We analyzed the TP53 codon 72 polymorphism in patients with type 1 diabetes (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
The region containing TP53 codon 72 polymorphism was amplified in a total volume of 15 μl, containing 20 ng of DNA template, 1.65 mM MgCl2 (Thermo Fisher Scientific, MA, USA), 200 μM dNTP (Thermo Fisher Scientific, MA, USA), 250 nM of each primer (Sigma-Aldrich, MO, USA), and 0.75 U FIREPol DNA polymerase with 1x buffer (Solis BioDyne, Tartu, Estonia)
Summary
Wild-type TP53 (tumor protein p53, more commonly known as P53) has been established as a tumor suppressor in human cancer as it plays an important role in the control of cell proliferation and death. The frequency of the Pro allele ranges from 70% among South Africans to 23% among Western Europeans. Pro is probably the ancient allele, but the reason for the high frequency of Arg among Europeans is unclear [7]. The Arg variant is a stronger apoptosis inducer while the Pro variant is a more powerful transcriptional activator that induces a higher level of cell cycle arrest [9]. A large number of studies have explored the role of TP53 codon 72 polymorphism in cancer providing mixed and confusing results. Considering increasingly appreciated role of P53 in the regulation of immune response and systemic inflammation, we were interested whether common functional TP53 polymorphism may affect diabetes complications and comorbidities
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