LncRNA SOX2OT rs9839776 Polymorphism Reduces Sepsis Susceptibility in Southern Chinese Children

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Abstract

Background

Sepsis in children is one of the main causes of death in pediatric intensive care units (PICUs); however, the pathogenesis of sepsis is not fully clear. Previous studies revealed that many genetic variations were related to sepsis susceptibility. A long non-coding RNA SOX2 overlapping transcript ( SOX2OT) may play a role in mitochondrial homeostasis and antioxidative activity, but the relationship between the lncRNA SOX2OT polymorphism and sepsis susceptibility has not been reported.

Methods

In this study, 474 pediatric sepsis patients and 678 healthy controls were recruited from southern China. After genotyping, the strength of the associations was evaluated through odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The SOX2OT rs9839776 T allele was associated with decreased susceptibility to sepsis in southern Chinese children (TT/CT vs CC adjusted OR = 0.778, 95% CI = 0.610–0.992; P = 0.0431). Moreover, the difference in susceptibility was greater in children of age >60 months (adjusted OR = 0.458, 95% CI = 0.234–0.896; P = 0.0225), survivors (adjusted OR = 0.758, 95% CI = 0.585–0.972; P = 0.0358), males (adjusted OR = 0.655, 95% CI = 0.479–0.894; P = 0.0077) and the sepsis subgroup (adjusted OR = 0.548, 95% CI = 0.343–0.876; P = 0.0120).

Conclusion

The rs9839776 T allele may contribute to decreased sepsis risk in Chinese children. Future studies with a larger sample size are needed to verify these results.

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Most cited references 29

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Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

R P Dellinger, Mitchell Levy, Andrew Rhodes … (2013)

Objective To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. Design A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Results Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao 2/Fio 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao 2/Fi o 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Conclusions Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients. Electronic supplementary material The online version of this article (doi:10.1007/s00134-012-2769-8) contains supplementary material, which is available to authorized users.

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Modular regulatory principles of large non-coding RNAs.

Mitchell Guttman, John Rinn (2012)

It is clear that RNA has a diverse set of functions and is more than just a messenger between gene and protein. The mammalian genome is extensively transcribed, giving rise to thousands of non-coding transcripts. Whether all of these transcripts are functional is debated, but it is evident that there are many functional large non-coding RNAs (ncRNAs). Recent studies have begun to explore the functional diversity and mechanistic role of these large ncRNAs. Here we synthesize these studies to provide an emerging model whereby large ncRNAs might achieve regulatory specificity through modularity, assembling diverse combinations of proteins and possibly RNA and DNA interactions.

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Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA.

Jes-Niels Boeckel, Nicolas Jaé, Andreas Heumüller … (2015)

Circular RNAs (circRNAs) are noncoding RNAs generated by back splicing. Back splicing has been considered a rare event, but recent studies suggest that circRNAs are widely expressed. However, the expression, regulation, and function of circRNAs in vascular cells is still unknown.

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Author and article information

Journal

Journal ID (nlm-ta): J Inflamm Res

Journal ID (iso-abbrev): J Inflamm Res

Journal ID (publisher-id): jir

Journal ID (pmc): jinres

Title: Journal of Inflammation Research

Publisher: Dove

ISSN (Electronic): 1178-7031

Publication date (Electronic): 10 December 2020

Publication date Collection: 2020

Volume: 13

Pages: 1095-1101

Affiliations

[1 ]Department of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou 510623, People’s Republic of China

[2 ]Department of Clinical Biological Resource Bank, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou 510623, People’s Republic of China

[3 ]Department of Blood Transfusion, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou 510623, People’s Republic of China

[4 ]Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou 510623, People’s Republic of China

Author notes

Correspondence: Xiaoqiong Gu; Jianping Tao Email guxiaoqiong@gwcmc.org; golou6354@163.com

[*]

These authors contributed equally to this work

Author information

Yongqin Yu http://orcid.org/0000-0002-0983-6635

Article

Publisher ID: 281760

DOI: 10.2147/JIR.S281760

PMC ID: 7735778

PubMed ID: 33328755

SO-VID: 92dfca95-574f-43eb-8e73-4a34a7eedc24

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 14 September 2020

Date accepted : 18 November 2020

Page count

Figures: 0, Tables: 8, References: 29, Pages: 7

Funding

Funded by: the Guangdong Provincial Science and Technology Plan;

Funded by: Guangzhou Medical and Health Technology Projects;

Funded by: Guangzhou Science and Technology Program Key Projects, open-funder-registry 10.13039/501100004000;

Funded by: Guangdong Natural Science Foundation, open-funder-registry 10.13039/501100003453;

Funded by: Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center Fund;

This study was funded by the Guangdong Provincial Science and Technology Plan (China, 2017A030223003), Guangzhou Medical and Health Technology Projects (China, 20191A011033 and 20191A011021), Guangzhou Science and Technology Program Key Projects (China, 201904010486 and 201804010035), Guangdong Natural Science Foundation (China, 2019A1515012061), and Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center Fund (China, grant number YIP-2018-019, GCP-2019-003, YIP-2019-050, GCP-2019-006).

LncRNA SOX2OT rs9839776 Polymorphism Reduces Sepsis Susceptibility in Southern Chinese Children

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Abstract

Background

Methods

Results

Conclusion

Related collections

Chinese Journal of Schistosomiasis Control

Most cited references 29

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

Modular regulatory principles of large non-coding RNAs.

Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA.

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