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

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

SUBMITTER: Zeng L

PROVIDER: S-EPMC4310192 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Zeng Ling L Du Juan J Gu Wei W Zhang An-qiang AQ Wang Hai-yan HY Wen Da-lin DL Qiu Lin L Yang Xue-tao XT Sun Jian-hui JH Zhang Mao M Hao Jiang J Jiang Jian-xin JX

Critical care (London, England) 20150109

<h4>Introduction</h4>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 exp ...[more]

PMID: 25572180

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Project description:ObjectiveThe aims of this study are to detect levels of AGEs and RAGE and SNPs for RAGE in vaginal tissues of women with POP and rats in a repair location, and to explore the relationship between AGEs-RAGE pathway and POP.MethodsThis study involved human vaginal tissues in fornix from 44 women with POP and 46 women without POP who were assigned to pelvic floor reconstruction or LAVH. The proteins of AGEs, collagen I, and RAGE were detected by immunohistochemistry and Western blot with appropriate primary antibodies. The entire RAGE gene of 24 women with POP and 25 controls were sequenced, and SNPs within were detected. Then, sixty 8-week-old female Sprague-Dawley rats subjected to abdominal defect were divided into three surgical pelvic floor reconstruction repair groups (n=20/group): A, repair with non-absorable prolene mesh; B, repair with absorbable SIS mesh; and C, a no repair control group. 3, 9, 15, and 21 months after operation, rats were sacrificed and the expression of AGEs, RAGE and collagen I in the tissues of repair location were detected in the various experimental groups. Statistical analysis included comparison of means (Student's t-test) and proportions (Chi-square test or Fisher test).ResultsBy both immunohistochemistry and Western blot, patients with POP showed higher protein expression of AGEs of POP than controls (P<0.05). In contrast, the expression of collagen I was lower in POP patients than in the control group (P<0.05). No differences in the expression of RAGE between the POP patients and controls were observed (P>0.05). In POP patients, the expression of collagen I decreased particularly in patients≥60 years old (P<0.05), but there were no different in the expression of AGEs and RAGE dependent on age (P>0.05). RAGE gene sequence variance analysis identified 18 variable loci, but only two of these were potential SNPs: rs184003 (1806), rs55640627 (2346) (P<0.05). Both rs184003 and rs55640627 are both intronic variants, indicating that they may not influence the structure of RAGE. In rat surgical repair model, group B showed a greater extent of abdominal prolapse than groups A and C (P<0.05). Consistent with this, the expression of AGEs in group B was higher than groups A and C (P<0.05), and collagen I in group B was lower than the two others, further supporting our notion that AGEs are inversely related to type I collagen content.ConclusionsIn summary, this study demonstrates that AGEs and RAGE might play important roles in the physiopathology of POP. Further studies are required to explore mechanisms of how AGEs-RAGE pathway may contribute to tissue degeneration and fragility in POP.

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

Publications

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

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