Factor SIRT1 Gene Polymorphism Is Associated With Type 2 Diabetic Nephropathy Early Metabolic Regulation

Background:In recent years, the prevalence rate of diabetes is increasing worldwide. Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. It’s a major cause of end-stage renal disease in western and Asian countries. And it’s the leading cause of death in diabetes. Diabetic nephropathy is a complex polygenic disease. The pathogenesis of DN is a result of interaction of multi gene, factors, and systems induced by hyperglycemia. Genetic factors have been proved to be an important factor for the occurrence of DN. Sirtuins, gene silent information regulator-2(SIR2) family, is an NAD dependent deacetylase enzymes. The sirtuins of mammal consists of7members:SIRT1-SIRT7. These members, especially SIRT1, play an important role in the pathogenesis in the regulation of age, viability, or age associated metabolic disease. It has being discovered in recent years that the family also has represented in kidney. Research found that the protective effect of energy restriction mediated by SIRT1participate in the aging process of the kidney. These discover suggest that, the SIRTl gene of mammal may be a susceptible gene of diabetic nephropathy. Also a study in Japan indicates that, SIRT1play an important role in susceptibility of diabetes nephropathy in Japanese individuals. There have been no reports of the correlation of SIRT1and early diabetic nephropathy at present.Objective:To explore the correlation between the gene polymorphism of metabolic regulation factor SIRT1and early type II diabetic nephropathy.Methods:Polymerase Chain reaction-single strand conformation polymorphic (PCR-SSCP), combined with direct sequencing, detecting the distribution of SIRT1in289unrelated cases of Han individuals in the coastal area of Shandong China. Subjects are divided into three groups:normal group (N group) of146cases, type2diabetic group (DM group) of66cases, and Microalbuminuria group (DN group) of77cases. Comparative analysis is used in each allele/genotype frequency. SPSS16.0statistical software for data analysis is applied.Results:l.The distribution of genotype frequencies of sirtl-rs2236319gene polymorphism complies with the Hardy-Weinberg equilibrium.There is no statistical significance between the distribution of gene frequency in diabetic group and control group (P=0.129); While there is statistical significance that the G allele frequency in diabetic group was significantly lower than the control group (P=0.038). Non conditional logistic regression analysis shows that, contrasted with the genotype AA, genotype AG and GG have no relationship with the risk of diabetes (P=0.261, OR0.692,95%CI:0.365-1.315and P=0.084, OR0.260,95%CI:0.570-1.197); while contrasted with the allele A, allele G relates with the decrease of the risk of diabetes (P=0.039, OR0.579,95%CI:0.344-0.973)2. There is no significant difference in the frequency distribution of genotype GG in early Microalbuminuria group and control group (P=0.166); The frequency distribution of allele G in early Microalbuminuria group is higher than the control group, while the difference has no statistical significance (P=0.066). Non conditional logistic regression analysis shows that, contrasted with the genotype AA, genotype AG and GG have no relationship with the risk of early diabetic nephropathy (P=0.650, OR1.152,95%CI:0.625-2.216and P=0.062, OR2.216,95%CI:0.960-5.115); while contrasted with the allele A, allele G also has no relationship with the risk of early diabetic nephropathy (P=0.067, OR1.482,95%CI:0.973-2.256)3.In diabetics, the distribution of genotype GG in early diabetic nephropathy is significantly higher than the type2diabetic group, and there is statistical significance (P=0.006). And there is statistical significance that the allele G frequency in early Microalbuminuria group is significantly higher than the type2diabetic group (P<0.001). Non conditional logistic regression analysis shows that, contrasted with the genotype AA, genotype GG relates with the increase of the risk of diabetes (P=0.007, OR9.514,95%CI:1.818-39.876), while the genotype AG has no relationship with the risk of early diabetic nephropathy (P=0.174, OR1.664,95%CI:0.799-3.468). Besides, contrasted with allele A, allele G relates with the increase of early diabetic nephropathy (P=0.001, OR2.559,95%CI:1.464-4.473)4. LDL-C、HbAlc and PBG are the risk factors to increase DN, if the regression coefficients of them are positive and the OR values are more than1; LDL-C、HbAlc and PBG are the protective factors to decrease DN, if the regression coefficients of them are negative and the OR values are less than1.Conclusion:1. The results of this study suggest that the allele G of SIRTl-rs2236319gene polymorphism relates with the decrease of the risk of diabetes; the genotype GG and allele G of SIRT1-rs2236319gene polymorphism relates with the increase of early diabetic nephropathy.2. Besides the genetic factor, the metabolic disorder of blood sugar and blood lipid are also the risk factors of type2diabetic nephropathy.