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MCP-1 rs1024611 多态性与 2 型糖尿病合并脓毒症遗传易感性的相关性研究。

Study on the association between the polymorphism of MCP-1 rs1024611 and the genetic susceptibility of type 2 diabetes with sepsis.

机构信息

Department of Endocrinology and Metabolism, The Second Affiliated Hospital,School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen, Guangdong, People's Republic of China.

Department of Critical Care Medicine,Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China.

出版信息

Medicine (Baltimore). 2022 Aug 12;101(32):e29903. doi: 10.1097/MD.0000000000029903.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) rs1024611 (-2518 A > G) polymorphism are associated with inflammatory diseases. In this study, we investigate the relationship between MCP-1 rs1024611 polymorphism and genetic susceptibility of type 2 diabetes mellitus (T2DM) with sepsis. Two hundred eighty-five patients with T2DM are divided into the diabetes with sepsis group (combined group, 113 cases) and the diabetes group (172 cases). Blood samples and corresponding clinical data were collected. MCP-1 rs1024611 polymorphism in blood samples was detected by pyrosequencing. Meanwhile, the expressions of MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in blood samples were detected by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The relationship between different genotypes of MCP-1 rs1024611 polymorphic locus and T2DM with sepsis was analyzed by combining with the clinical data of the patients. The frequencies of rs1024611 AG/GG genotypes and G allele in T2DM with sepsis group were significantly higher than those in T2DM patients without sepsis (P = .004 for AG/GG vs AA genotypes; P = .037 for G allele vs A allele). Subgroup analysis showed that the rs1024611 G allele frequency in the septic shock group was significantly higher than the general sepsis group (P = .02). The expressions of MCP-1 and TNF-α in GG genotypes in T2DM with sepsis group were significantly higher than AA or GA genotypes (P < .05). This study preliminarily showed that the rs1024611 A > G polymorphism within the promoter region of MCP-1 gene can upregulate the expression of MCP-1 gene and proinflammatory cytokine TNF-α, which ultimately contributed to the predisposition and progression of T2DM with sepsis.

摘要

单核细胞趋化蛋白-1(MCP-1)rs1024611(-2518A>G)多态性与炎症性疾病有关。本研究旨在探讨 MCP-1 rs1024611 多态性与合并脓毒症的 2 型糖尿病(T2DM)遗传易感性的关系。将 285 例 T2DM 患者分为糖尿病合并脓毒症组(合并组,113 例)和糖尿病组(172 例)。采集血样及相应临床资料,采用焦磷酸测序法检测血样中 MCP-1 rs1024611 多态性,实时定量聚合酶链反应和酶联免疫吸附试验分别检测血样中 MCP-1、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和 IL-6 的表达。结合患者的临床资料,分析不同 MCP-1 rs1024611 多态性位点基因型与 T2DM 合并脓毒症的关系。T2DM 合并脓毒症组 rs1024611 AG/GG 基因型及 G 等位基因频率明显高于 T2DM 无脓毒症患者(AG/GG 与 AA 基因型相比,P=0.004;G 等位基因与 A 等位基因相比,P=0.037)。亚组分析显示,脓毒性休克组 rs1024611 G 等位基因频率明显高于一般脓毒症组(P=0.02)。T2DM 合并脓毒症组 GG 基因型 MCP-1 和 TNF-α 的表达明显高于 AA 或 GA 基因型(P<0.05)。本研究初步表明,MCP-1 基因启动子区 rs1024611A>G 多态性可上调 MCP-1 基因及促炎细胞因子 TNF-α的表达,进而导致 T2DM 合并脓毒症的易感性和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8df2/9371515/5e63c6e87439/medi-101-e29903-g001.jpg

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