Different Roles of Codon 72 Polymorphism in Type 2 Diabetes and Its Complications: Evidence from a Case-Control Study on a Chinese Han Population.

Objective: The purpose of this study was to investigate the relationships between (rs1042522) polymorphism and susceptibility to type 2 diabetes (T2DM) and its related complications.

Methods: The 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 differed in T2DM patients from the controls, with a moderately increased proportion of variant carriers ( and genotypes) (88.3% vs 81.2%, =0.022; OR=1.089, 95% CI=1.018-1.164). T2DM patients with genotype had significantly decreased prevalences of diabetic neuropathy and retinopathy compared to those without (6.5% vs 19.4%, =0.018 and 14.8% vs 30.7%, =0.018, respectively). T2DM patients with genotype had higher mtDNA content and mtRNA expression level than those who were not genotype (<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 polymorphism with susceptibility to T2DM, and the homozygous genotype of this gene locus might be a protective factor for diabetic complications. Those results suggested that the 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.