Objective: The purpose of this study was to investigate the relationships between TP53 Pro72Arg  (rs1042522) polymorphism and susceptibility to type 2 diabetes (T2DM) and its related complications.
Methods: The TP53 Pro72Arg  polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 206 T2DM patients and 446 healthy controls. Mitochondrial DNA (mtDNA) content, mtDNA transcriptional level and large-scale mtDNA deletion were evaluated in leukocytes of T2DM patients using fluorescence-based quantitative PCR (FQ-PCR), reverse transcriptase-quantitative PCR (RT-qPCR) and long-range PCR approaches, respectively. The data of our study were processed by GraphPad Prism software (version 7.00).
Results: The distribution of TP53 Pro72Arg  differed in T2DM patients from the controls, with a moderately increased proportion of TP53 Arg72  variant carriers (Pro/Arg  and Arg/Arg  genotypes) (88.3% vs 81.2%, p =0.022; OR=1.089, 95% CI=1.018– 1.164). T2DM patients with Arg/Arg  genotype had significantly decreased prevalences of diabetic neuropathy and retinopathy compared to those without (6.5% vs 19.4%, p =0.018 and 14.8% vs 30.7%, p =0.018, respectively). T2DM patients with Arg/Arg  genotype had higher mtDNA content and mtRNA expression level than those who were not Arg/Arg  genotype (p < 0.05 for all), and we did not observe mtDNA 4977-base pair (bp) deletion mutations in the leukocytes of T2DM patients.
Conclusion: There was a significant association of the TP53 Pro72Arg  polymorphism with susceptibility to T2DM, and the homozygous Arg/Arg  genotype of this gene locus might be a protective factor for diabetic complications. Those results suggested that the TP53 Arg72  variant had a different association with type 2 diabetes and its complications, and it might be related to mtDNA maintenance of the TP53 Arg72 variant under hyperglycemia-induced stress.
Keywords: TP53, type 2 diabetes mellitus, complication, mtDNA content, mtRNA, mtDNA maintenance