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SIRT1基因多态性对糖尿病足易感性和严重程度的影响。

Influence of SIRT1 polymorphisms for diabetic foot susceptibility and severity.

作者信息

Peng Yi, Zhang Guishan, Tang Hongxia, Dong Luling, Gao Chunbin, Yang Xiuhong, Peng Ying, Xu Yanrong

机构信息

Department of Endocrinology, The First Hospital of Zhangjiakou, Zhangjiakou, Hebei, China.

出版信息

Medicine (Baltimore). 2018 Jul;97(28):e11455. doi: 10.1097/MD.0000000000011455.

DOI:10.1097/MD.0000000000011455
PMID:29995800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6076161/
Abstract

The present study aimed to explore the influence of sirtuin 1 (SIRT1) polymorphisms (rs12778366 and rs3758391) on diabetic foot (DF) susceptibility and severity in patients with type 2 diabetes mellitus (T2DM).This case-control study recruited 142 patients with DF, 148 patients with T2DM, and 148 healthy controls. SIRT1 gene polymorphisms were sequenced by polymerase chain reaction (PCR) and direct sequencing method. The relative expression of SIRT1 mRNA was estimated using quantitative real-time PCR (qRT-PCR) assay. Odds ratio (OR) with 95% confidence interval (95% CI) were used to represent the association of SIRT1 polymorphisms with DF susceptibility and severity. The results were adjusted using logistic regression analysis.C allele of rs12778366 polymorphism was significantly correlated with reduced DF susceptibility which deriving from healthy controls (adjusted OR = 0.364, 95% CI = 0.158-0.835) so was patients with T2DM (P = .047, OR = 0.591, 95%CI = 0.349-0.998), but the results became nonsignificant adjusted by clinical features (adjusted OR = 0.654, 95% CI = 0.391-1.094). We failed to find any significant association between rs3758391 polymorphisms and T2DM, DF susceptibility. No significant association has been discovered between SIRT1 polymorphisms and DF severity or characteristics. In addition, compared to healthy control and T2DM cases, patients with DF exhibited significant downregulation of SIRT1. The 2 studied polymorphisms had no effects on its gene expression (P > .05 for all).SIRT1 rs12778366 polymorphism C allele might act as a protective factor for DF onset.

摘要

本研究旨在探讨沉默调节蛋白1(SIRT1)基因多态性(rs12778366和rs3758391)对2型糖尿病(T2DM)患者糖尿病足(DF)易感性及严重程度的影响。这项病例对照研究纳入了142例DF患者、148例T2DM患者和148例健康对照者。采用聚合酶链反应(PCR)和直接测序法对SIRT1基因多态性进行测序。运用定量实时PCR(qRT-PCR)检测法评估SIRT1 mRNA的相对表达量。采用比值比(OR)及95%置信区间(95%CI)来表示SIRT1基因多态性与DF易感性及严重程度的关联。结果经逻辑回归分析校正。rs12778366多态性的C等位基因与DF易感性降低显著相关,健康对照者中(校正OR = 0.364,95%CI = 0.158 - 0.835)以及T2DM患者中(P = 0.047,OR = 0.591,95%CI = 0.349 - 0.998)均如此,但经临床特征校正后结果无统计学意义(校正OR = 0.654,95%CI = 0.391 - 1.094)。我们未发现rs3758391多态性与T2DM、DF易感性之间存在任何显著关联。未发现SIRT1基因多态性与DF严重程度或特征之间存在显著关联。此外,与健康对照者和T2DM患者相比,DF患者的SIRT1表达显著下调。所研究的两种多态性对其基因表达均无影响(所有P均>0.05)。SIRT1 rs12778366多态性的C等位基因可能是DF发病的保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2260/6076161/6ff41b3e82b4/medi-97-e11455-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2260/6076161/747ae9f97ab2/medi-97-e11455-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2260/6076161/6ff41b3e82b4/medi-97-e11455-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2260/6076161/747ae9f97ab2/medi-97-e11455-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2260/6076161/6ff41b3e82b4/medi-97-e11455-g007.jpg

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In type 2 diabetes induced by cigarette smoking, activation of p38 MAPK is involved in pancreatic β-cell apoptosis.
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