International Journal of General Medicine (Aug 2021)
Different Roles of TP53 Codon 72 Polymorphism in Type 2 Diabetes and Its Complications: Evidence from a Case-Control Study on a Chinese Han Population
Abstract
Dong Guo,1 Liang Fang,2 Xuelai Yu,3 Congyang Wang,4 Yan Wang,4 Wenwen Guo4 1Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 4Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of ChinaCorrespondence: Wenwen Guo; Yan WangDepartment of Pathology, The Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, People’s Republic of ChinaTel +86-25-58509910; +86-25-58509909Email [email protected]; [email protected]: 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
