Transcriptional Co-Activator P300 And Silent Information Regulator 1 SIRT 1 Polymorphism Correlate With Diabetic Kidney Disease

Objective:Diabetic kidney disease is one of the most severe complications of diabetes mellitus, and is a leading cause of end-stage renal disease of all ages across all ethnic groups. However, the precise pathogenesis of diabetic kidney disease is not entirely clear. Current studies suggest that histone acetylation modifications play a key role in the occurrence and the development of diabetic kidney disease. The study intends to investigate the possible association between in a cohort of Chinese type 2 diabetic patients.Method:We conducted a case-control study in Chinese Han population located in the Chongqing region of China. Patients with Type 2 diabetes mellitus were recruited from Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University from March 2013 to December 2014. Genotyping of p300 and SIRT 1 polymorphism was performed using an allelic discrimination assay with TaqMan probes. Statistical analysis was conducted to figure out the risk factors of diabetic kidney disease.Results:1.In p300 gene, genotype frequencies of AA, AG and GG were 79.6%,19.8% and 0.6%. In SIRT 1 gene, genotype frequencies of TT, TC and CC were 26.7%,52.5% and 20.8%. The distribution of genotype frequencies of p300 and SIRT 1 gene polymorphism complies with the Hardy-Weinberg equilibrium.2. The frequency distribution of allele G was higher in DKD group and patients with allele G have a higher risk for the occurrence of diabetic kidney disease.3. In female patients or patients under the age of 65, patients with genotype of AG or GG has a higher risk than patients with AA for the occurrence of diabetic kidney disease.4. Patients with genotype of AG or GG have a higher risk to develop a more serious diabetic kidney disease than patients with AA genotype, especially in patients over the age of 65.5. SIRT 1 rs4746720 allele C is a risk factor of urinary Alb/Cr.6. Patients with allele G and the genotype of TC have a higher risk for the occurrence of diabetic kidney disease, while patients with allele G and the genotype of TT has a higher risk to develop a more serious diabetic kidney disease.Conclusion:Transcriptional co-activator p300 gene polymorphism is associated with the occurrence and progression of diabetic kidney. In addition, the p300 gene interacts with SIRT 1 gene, participating in the development of albuminuria in patients with type 2 diabetes mellitus.