A Functional Variant of Lipopolysaccharide Binding Protein Predisposes to Sepsis and Organ Dysfunction in Patients with Major Trauma

Gu, Wei; Zhang, Anqiang; Zhang, Mao; Zhang, Lianyang; Du, Debin; Huang, Suna; Jiang, Jianxin

doi:10.1097/sla.0b013e3182389515

Cited by 40 publications

(37 citation statements)

References 33 publications

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“…Leira et al [32] have validated that the fibrinogen is an independent predictor of early neurologic deterioration in ICH patients. LBP is one of the acute phase immunologic response proteins for bacterial infection known to be involved in regulating LPS-dependent monocyte response [33]. As described above, the combination of LPS and CD14 can initiate inflammation response which is mediated by LBP, and many studies indicate that LBP is a marker of acute inflammation in patients with trauma [34].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics

Zhang²,

et al. 2017

Clin Proteom

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BackgroundThe systematic mechanisms of acute intracerebral hemorrhage are still unknown and unverified, although many recent researches have indicated the secondary insults. This study was aimed to disclose the pathological mechanism and identify novel biomarker and therapeutic target candidates by plasma proteome.MethodsPatients with AICH (n = 8) who demographically matched healthy controls (n = 4) were prospectively enrolled, and their plasma samples were obtained. The TMT-LC–MS/MS-based proteomics approach was used to quantify the differential proteome across plasma samples, and the results were analyzed by Ingenuity Pathway Analysis to explore canonical pathways and the relationship involved in the uploaded data.ResultsCompared with healthy controls, there were 31 differentially expressed proteins in the ICH group (P < 0.05), of which 21 proteins increased while 10 proteins decreased in abundance. These proteins are involved in 21 canonical pathways. One network with high confidence level was selected by the function network analysis, in which 23 proteins, P38MAPK and NFκB signaling pathways participated. Upstream regulator analysis found two regulators, IL6 and TNF, with an activation z-score. Seven biomarker candidates: APCS, FGB, LBP, MGMT, IGFBP2, LYZ, and APOA4 were found. Six candidate proteins were selected to assess the validity of the results by subsequent Western blotting analysis.ConclusionOur analysis provided several intriguing pathways involved in ICH, like LXR/RXR activation, acute phase response signaling, and production of NO and ROS in macrophages pathways. The three upstream regulators: IL-6, TNF, LPS, and seven biomarker candidates: APCS, APOA4, FGB, IGFBP2, LBP, LYZ, and MGMT were uncovered. LPS, APOA4, IGFBP2, LBP, LYZ, and MGMT are novel potential biomarkers in ICH development. The identified proteins and pathways provide new perspectives to the potential pathological mechanism and therapeutic targets underlying ICH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9149-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics

Zhang²,

et al. 2017

Clin Proteom

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“…Recent correlations between genetic variations and clinical conditions or outcomes 3–5 raise questions as to whether single nucleotide polymorphisms (SNPs) are associated with HTS development. A study by van Tiel and colleagues found that a SNP in the p27 kip1 gene, −838C>A, (rs36228499) was associated with a decreased risk of in-stent restenosis of cardiac stents.…”

Section: Introductionmentioning

confidence: 99%

Genetic Risk Factors for Hypertrophic Scar Development

Thompson

Hocking

Honari

et al. 2013

Journal of Burn Care & Research

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Objective Hypertrophic scars (HTS) occur in 30–72% patients following thermal injury. Risk factors include skin color, female gender, young age, burn site, & burn severity. Recent correlations between genetic variations and clinical conditions suggest that single nucleotide polymorphisms (SNPs) may be associated with HTS formation. We hypothesized that a SNP in the p27kip1 gene (rs36228499) previously associated with decreased restenosis after coronary stenting would be associated with lower Vancouver scar scale (VSS) measurements and decreased itching. Methods Patient & injury characteristics were collected from adults with thermal burns. VSS scores were calculated at 4–9 months following injury. Genotyping was performed using real time PCR. Logistic regression was used to determine risk factors for hypertrophic scar as measured by a VSS score >7. Results 300 subjects had a median age of 39 years (range 18–91); 69% were male & median burn size was 7% TBSA (range 0.25–80). Consistent with literature, the p27kip1 variant SNP had an allele frequency of 40%, but was not associated with reduced HTS formation or lower itch scores in any genetic model. HTS formation was associated with American Indian/Alaskan Native race (OR, 12.2; P=0.02), facial burns (OR, 9.4; P=0.04), and burn size ≥20% TBSA (OR, 1.99; P=0.03). Conclusions Whereas the p27kip1 SNP may protect against vascular fibroproliferation, the effect cannot be generalized to cutaneous scars. Our study suggests that American Indian/Alaskan Native race, facial burns, and higher %TBSA are independent risk factors for HTS. The American Indian/Alaskan Native association suggests that there are potentially yet-to-be-identified genetic variants.

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“…DNA concentration in all samples was determined by ultraviolet spectrophotometry, adjusted to a concentration of 40 μg/mL with sterile distilled water and stored at −80 • C. Pyrosequencing was used for genotyping. 16 Genotyping was performed in a blinded fashion without knowledge of the patients' clinical data, and approximately 10% of the samples were genotyped in duplicate to monitor genotyping quality.…”

Section: Genotypingmentioning

confidence: 99%

“…[9][10][11][12][13][14][15] Growing evidence indicates that genetic variants, particularly single nucleotide polymorphisms (SNPs), are critical determinants for interindividual differences in both inflammatory responses and clinical outcomes in patients with trauma. 16,17 Because small variation in the quantity of miRNAs may have an effect on thousands of target mRNAs and result in diverse functional consequences, SNPs in miRNA sequences have become a new research topic in this field. Up to now, the majority of studies have been focused on cancer susceptibility.…”

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confidence: 99%

Genetic Variants of microRNA Sequences and Susceptibility to Sepsis in Patients With Major Blunt Trauma

Zhang

Gu²,

Zhang³

et al. 2015

Annals of Surgery

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A Functional Variant of Lipopolysaccharide Binding Protein Predisposes to Sepsis and Organ Dysfunction in Patients with Major Trauma

Abstract: The rs2232618 polymorphism is a functional SNP and confers host susceptibility to sepsis and multiple organ dysfunction in patients with major trauma.

Cited by 40 publications

References 33 publications

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics

Genetic Risk Factors for Hypertrophic Scar Development

Genetic Variants of microRNA Sequences and Susceptibility to Sepsis in Patients With Major Blunt Trauma

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