Correlation Between Polymorphisms of the SIRT1 Gene microRNA Target Sites and Diabetic Nephropathy.

Abstract

Objective: To study the correlations between the genotypic and allelic frequencies of the Sirtuin 1 (SIRT1) gene rs182180876, rs4746720, and rs2234975 loci and susceptibility to diabetic nephropathy. Methods: We used Sanger sequencing to analyze the genotypes of the rs182180876, rs4746720, and rs2234975 loci within the SIRT1 gene in 280 diabetic nephropathy patients and 280 diabetic patients without kidney disease who acted as the control group. Plasma SIRT1 levels were analyzed by enzyme-linked immunosorbent assay, and hsa-miR-126-5p, hsa-miR-2115-3p, and hsa-miR-200a-3p in plasma were detected by quantitative real-time polymerase chain reaction levels. Results: SIRT1 rs182180876 locus G allele carriers were 3.21 times more likely to suffer from diabetic nephropathy than carriers of the C allele (95% confidence interval [CI]: 2.08-4.95, p < 0.01). Carriers of the T allele at the rs2234975 locus had a higher risk of diabetic nephropathy than carriers of the C allele (odds ratio [OR] = 2.02, 95% CI: 1.36-3.01, p < 0.01). The SIRT1 three locus CCC haplotype was associated with a decreased risk of diabetic nephropathy (OR = 0.24, 95% CI: 0.13-0.46, p < 0.01), and the CTT haplotype was associated with an increased risk of diabetic nephropathy (OR = 3.19, 95% CI: 1.41-7.22, p = 0.01). The plasma SIRT1 levels of patients with diabetic nephropathy were lower than those of the control group (p < 0.001). The plasma SIRT1 levels were lower in SIRT1 rs182180876 locus G allele carriers, rs4746720 locus T allele carriers, and rs2234975 locus T allele carriers than in carriers of the alternate alleles. Diabetic nephropathy patients' plasma hsa-miR-126-5p, hsa-miR-2115-3p, and hsa-miR-200a-3p levels were higher than those of the control group (p < 0.001). Plasma SIRT1 levels were negatively correlated with hsa-miR-126-5p, hsa-miR-2115-3p, and hsa-miR-200a-3p levels (r = -0.90, -0.77, -0.92, -0.83, -0.87, -0.87). Conclusion: The SIRT1 loci rs182180876, rs4746720, and rs2234975 single nucleotide polymorphisms are significantly associated with the risk of diabetic nephropathy. Clinical Trials.gov ID: 2016-ZJ002-01.