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2 型糖尿病中的氧化应激基因:与糖尿病肾病的关联。

Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease.

机构信息

Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.

Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.

出版信息

Oxid Med Cell Longev. 2021 Sep 2;2021:2531062. doi: 10.1155/2021/2531062. eCollection 2021.

Abstract

Diabetic type 2 patients compared to nondiabetic patients exhibit an increased risk of developing diabetic kidney disease (DKD), the leading cause of end-stage renal disease. Hyperglycemia, hypertension, oxidative stress (OS), and genetic background are some of the mechanisms and pathways implicated in DKD pathogenesis. However, data on OS pathway susceptibility genes show limited success and conflicting or inconclusive results. Our study is aimed at exploring OS pathway genes and variants which could be associated with DKD. We recruited 121 diabetes mellitus type 2 (DM2) patients with DKD (cases) and 220 DM2, non-DKD patients (control) of Greek origin and performed a case-control association study using genome-wide association data. PLINK and EIGENSOFT were used to analyze the data. Our results indicate 43 single nucleotide polymorphisms with their 21 corresponding genes on the OS pathway possibly contributing or protecting from DKD: SPP1, TPO, TTN, SGO2, NOS3, PDLIM1, CLU, CCS, GPX4, TXNRD2, EPHX2, MTL5, EPX, GPX3, ALOX12, IPCEF1, GSTA, OXR1, GPX6, AOX1, and PRNP. Therefore, a genetic OS background might underlie the complex pathogenesis of DKD in DM2 patients.

摘要

与非糖尿病患者相比,2 型糖尿病患者发生糖尿病肾病(DKD)的风险增加,DKD 是终末期肾病的主要原因。高血糖、高血压、氧化应激(OS)和遗传背景是 DKD 发病机制中涉及的一些机制和途径。然而,关于 OS 途径易感基因的数据显示成功率有限,结果存在冲突或不一致。我们的研究旨在探索可能与 DKD 相关的 OS 途径基因和变异。我们招募了 121 名 2 型糖尿病(DM2)伴 DKD(病例)和 220 名 DM2、非 DKD 患者(对照),并使用全基因组关联数据进行病例对照关联研究。PLINK 和 EIGENSOFT 用于分析数据。我们的结果表明,OS 途径中的 43 个单核苷酸多态性及其 21 个相应基因可能导致或预防 DKD:SPP1、TPO、TTN、SGO2、NOS3、PDLIM1、CLU、CCS、GPX4、TXNRD2、EPHX2、MTL5、EPX、GPX3、ALOX12、IPCEF1、GSTA、OXR1、GPX6、AOX1 和 PRNP。因此,遗传 OS 背景可能是 DM2 患者 DKD 复杂发病机制的基础。

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