Rs1800625 in the receptor for advanced glycation end products gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with major trauma

Ling Zeng, Juan Du, Wei Gu, An-qiang Zhang, Hai-yan Wang, Da-lin Wen, Lin Qiu, Xue-tao Yang, Jian-hui Sun, Mao Zhang, Jiang Hao, Jian-xin Jiang, Ling Zeng, Juan Du, Wei Gu, An-qiang Zhang, Hai-yan Wang, Da-lin Wen, Lin Qiu, Xue-tao Yang, Jian-hui Sun, Mao Zhang, Jiang Hao, Jian-xin Jiang

Abstract

Introduction: The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, it plays pivotal roles in the pathogenesis of sepsis in several ways. Our previous study showed that rs1800625 (-429T/C) revealed a strong clinical relevance with sepsis morbidity rate and multiple organ dysfunction syndrome (MODS) in patients with major trauma. In this study, we enlarged the sample size, added two validation populations and examined the expression of RAGE on the surface of peripheral leukocytes to ex vivo lipopolysaccharide (LPS) stimulation in subjects with different genotypes.

Methods: Rs1800625 was genotyped using pyrosequencing in 837 Chinese Han patients with major trauma in Chongqing. We then validated the clinical relevance in 340 Zhejiang and 347 Yunnan patients. The expression of RAGE on the surface of peripheral blood mononuclear cells was measured by flow cytometric analysis.

Results: The results indicated that rs1800625 was significantly associated with sepsis morbidity rate and MODS in patients with major trauma in the Chongqing, Zhejiang and Yunnan districts. Patients with CC genotype had lower sepsis morbidity rate and MODS after major trauma. Furthermore, patients with CC genotype had significantly higher RAGE expression (P = 0.009).

Conclusions: The rs1800625 polymorphism is a functional single nucleotide polymorphism and confers host susceptibility to sepsis and MODS in patients with major trauma.

Figures

Figure 1
Figure 1
Association of the rs1800625 with LPS-induced expression of RAGE protein. The whole blood samples were collected from 42 healthy volunteers (TT: N = 32, TC: N = 8, CC: N = 2). The RAGE expression on the peripheral leukocytes was assayed using flow cytometry and was presented as MFI. One-way ANOVA was used to assess statistical significance. P = 0.009 for dominant association (CC + TC vs. TT). ANOVA, analysis of variance; LPS lipopolysaccharide; RAGE, the receptor for advanced glycation end products.

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Source: PubMed

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