Correlations between SIRT1 gene polymorphisms and diabetic kidney disease

Zai-Gang Yang,Yue Zhang,Xin-Ge Yue,Fei Liu,Gui-Jun Qin

doi:10.1098/rsos.171871

Abstract

To investigate the correlations between SIRT1 gene polymorphisms and diabetic kidney disease (DKD). There were 150 patients with DKD in the observation group (urinary albumin excretion rate (UAER) ≥ 300 mg 24 h−1), and 160 patients with a more than 10 year history of type 2 diabetes but without retinopathy and DKD (UAER < 30 mg 24 h−1) in the control group. Genotypes of three tagged single-nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1 gene in the two groups were detected. Risks of DKD for patients with the GG and GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92 times higher than that for AA genotype carriers, respectively. The risk of DKD for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21 times higher than that for AA and for AA + AG genotype carriers, respectively, and the risk of DKD for patients with allele G was 0.66 times higher than that for allele A carriers. There was no significant difference in genotype frequency of rs4746720 locus gene polymorphisms between the observation and control groups. The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype GG and allele G in the rs3818292 locus can decrease the risk of DKD.

Highlights

Diabetic kidney disease (DKD) is one of the most severe microvascular complications of diabetes mellitus, which even happens to patients who have good long-term glycaemic control
Single-nucleotide polymorphism (SNP) data of the SIRT1 gene of the Chinese population were obtained through the HapMap database [10], and the data were imported into the HAPLOVIEW software [11]
The result showed that Haemoglobin A1C (HbA1C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and body mass index (BMI) had an influence on the occurrence of DKD, and that HDL level had a negative relation with the onset of DKD

Summary

Introduction

Diabetic kidney disease (DKD) is one of the most severe microvascular complications of diabetes mellitus, which even happens to patients who have good long-term glycaemic control. About 20%–40% of diabetic patients develop DKD, and DKD is the primary cause of end-stage renal disease (ESRD) [1,2]. Type I and II diabetes can cause kidney disease, and even lead to ESRD. [3] The pathogenesis of DKD is concealed, and DKD can lead to irreversible end-stage renal failure, which severely affects the life expectancy and quality of life of diabetics [4]. The pathogenesis of DKD is not yet fully understood, and previous studies have suggested that glucose, lipid metabolism disorders, oxidative stress, inflammatory reactions and multiple cytokines are closely related to the onset of DKD [5,6]. This study was to investigate the correlations between SIRT1 gene polymorphisms and DKD

Materials

DNA extraction

SIRT1 gene polymorphism detection

Sequencing verification

Biochemical detection

Statistical analysis

Basic data

Comparison of the SIRT1 gene between two groups

Regression analysis of correlation factors

Discussion

Findings

17. Kume S et al 2007 SIRT1 inhibits transforming