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

Zhang, Anqiang; Gu, Weijun; Zhang, Lianyang; Du, Debin; Zhang, Mao; Jiang, Hao; Yue, Cai-li; Jiang, Jianxin

doi:10.1097/sla.0000000000000687

Cited by 36 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microarray analyses, next-generation sequencing, and quantitative RT-PCR are important tools in developing biomarkers [15–21, 50, 51, 53, 57, 71, 97, 107, 119–131]. To date, candidate regulatory RNAs are limited to miRNAs.…”

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

View full text Add to dashboard Cite

BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

View full text Add to dashboard Cite

show abstract

“…Furthermore, various studies have identified miRNAs that are dysregulated in patients with sepsis [29][30][31][32]. More recent studies have implicated miRNAs in the host defense against trauma [33][34][35]. In general, these studies have not been correlated with the underlying monocyte phenotype.…”

Section: The Future Of Monocyte Biology In the Surgical Patientmentioning

confidence: 95%

Past, Present, and Future of Augmentation of Monocyte Function in the Surgical Patient

Galbraith

Carter

Polk

2016

Surgical Infections

View full text Add to dashboard Cite

Early studies have been promising in identifying patients who are likely to benefit from monocyte augmentation; i.e., those with low HLA-DR or ex-vivo tumor necrosis factor (TNF)-α production. The surgeon remains incompletely equipped to enhance monocyte function consistently and specifically in order to reduce the mortality rate. Although there is little evidence to support the routine use of any of these immunotherapies, the issues of patient selection, timing of administration, and treatment duration have hampered any true answers to this important clinical problem. The challenge remains in identifying the right patients, at the right time, to receive the right therapy.

show abstract

“…Han Chinese from the Department of Trauma Surgery in Daping Hospital between August, 2010 and March, 2016. Demographic and clinical information were derived from the electronic medical record and trauma biobank, as previously described [12]. Patients enrolled in the current study meet the following criteria: (1) aged from 18 to 65 years, (2) injury severity score (ISS) more than 16; and (3) survival ≥48 hours in hospital.…”

Section: Patient Recruitmentmentioning

confidence: 99%

“…For example, rs4957796 within FER gene and rs5743551 located into the promoter region of TLR1 might affect the risk of sepsis [9,11]. Moreover, rs4919510 in MIR608 and rs2232618 in the coding region of LBP gene were both functional variants and conferred susceptibility to sepsis after trauma [12,13]. Therefore, delineating genetic heterogeneity for sepsis might contribute to the diagnostic approaches and therapeutic trials among trauma patients.…”

Section: Introductionmentioning

confidence: 99%

Polygenic risk score for early prediction of sepsis risk in the polytrauma screening cohort

Wen

Sun

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Increasing genetic variants associated with sepsis have been identified by candidate-gene and genome-wide association studies, but single variant conferred minimal alterations in risk prediction. Our aimed to evaluate whether a weighted genetic risk score (wGRS) that aggregate information from multiple variants could improve risk discrimination of traumatic sepsis.Methods: 64 genetic variants potential relating to sepsis were genotyped in Chinese trauma cohort. Genetic variants with mean decrease accuracy (MDA) > 1.0 by random forest algorithms were selected to construct the multilocus wGRS. Area under curve (AUC) and Net reclassification improvement (NRI) were adopted to evaluate the discriminatory and reclassification ability of wGRS.Results: Seventeen variants were extracted to construct the wGRS in 883 trauma patients. The wGRS was significantly associated with sepsis after trauma (OR = 2.19, 95%CI = 1.53–3.15, P = 2.01 × 10− 5) after adjusted by age, sex, and ISS. Patients with higher wGRS have an increasing incidence of traumatic sepsis (Ptrend=6.81 × 10− 8), higher SOFA (Ptrend=5.00 × 10− 3) and APACHE II score (Ptrend=1.00 × 10− 3). The AUC of risk prediction model incorporating wGRS into the clinical variables was 0.768 (95%CI = 0.739–0.796), with an increase of 3.40% (P = 8.00 × 10− 4) versus clinical factors-only model. Furthermore, the NRI increased 25.18% (95%CI = 17.84–32.51%) (P = 6.00 × 10− 5).Conclusions: Our finding indicated that genetic variants could enhance the predictive power of risk model for sepsis and highlighted the application among trauma patients, suggesting that the sepsis risk assessment model will be a promising screening and prediction tool for high risk population.

show abstract

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

Abstract: Our results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic biomarker for sepsis in patients with major trauma. Further characterization of miRNA SNPs may open new avenues for studying sepsis and developing novel therapeutic approaches.

Cited by 36 publications

References 41 publications

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Past, Present, and Future of Augmentation of Monocyte Function in the Surgical Patient

Polygenic risk score for early prediction of sepsis risk in the polytrauma screening cohort

Contact Info

Product

Resources

About