Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP

Colín-Castro, Claudia Adriana; Franco-Cendejas, Rafael; Rocha-González, Héctor Isaac; Cruz-Arenas, Esteban; Leyva-García, Norberto; Sánchez-Sánchez, Roberto; Leyva‐Gómez, Gerardo; Gómez, Rocío; Muñoz, Balam; Cortés, Hernán; Magaña, Jonathan J.

doi:10.1038/s41435-021-00121-z

Cited by 4 publications

(3 citation statements)

References 64 publications

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“…One of the most studied is TLR4, that recognizes LPS molecule. Genetic polymorphisms associated with this molecule have been associated with an increased risk of critical illness such as sepsis or multiple organ failure after trauma [ 8 , 9 ]. Aside from TLR4, many other PPR have been implicated in the pathophysiology of critical illness ( Figure 2 ) and strategies to modulate them might, in the future, help reprogram the immune response in the context of critical illness.…”

Section: Why Monitor the Immune System During Critical Illness?mentioning

confidence: 99%

Monitoring of the Forgotten Immune System during Critical Illness—A Narrative Review

Parlato

Gomes

Fernandes³

2022

Medicina

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Immune organ failure is frequent in critical illness independent of its cause and has been acknowledged for a long time. Most patients admitted to the ICU, whether featuring infection, trauma, or other tissue injury, have high levels of alarmins expression in tissues or systemically which then activate innate and adaptive responses. Although necessary, this response is frequently maladaptive and leads to organ dysfunction. In addition, the counter-response aiming to restore homeostasis and repair injury can also be detrimental and contribute to persistent chronic illness. Despite intensive research on this topic in the last 40 years, the immune system is not routinely monitored in critical care units. In this narrative review we will first discuss the inflammatory response after acute illness and the players of maladaptive response, focusing on neutrophils, monocytes, and T cells. We will then go through commonly used biomarkers, like C-reactive protein, procalcitonin and pancreatic stone protein (PSP) and what they monitor. Next, we will discuss the strengths and limitations of flow cytometry and related techniques as an essential tool for more in-depth immune monitoring and end with a presentation of the most promising cell associated markers, namely HLA-DR expression on monocytes, neutrophil expression of CD64 and PD-1 expression on T cells. In sum, immune monitoring critically ill patients is a forgotten and missing piece in the monitoring capacity of intensive care units. New technology, including bed-side equipment and in deep cell phenotyping using emerging multiplexing techniques will likely allow the definition of endotypes and a more personalized care in the future.

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Section: Why Monitor the Immune System During Critical Illness?mentioning

confidence: 99%

Monitoring of the Forgotten Immune System during Critical Illness—A Narrative Review

Parlato

Gomes

Fernandes³

2022

Medicina

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“…It focuses on the integration and visualization of all the available information from different platforms. In silico approaches to short-listing the candidate genes provide the opportunity to reduce the workload of downstream laboratory experiments and the costs involved [ 10 ]. The recently released whole genome sequence of bread wheat ( Triticum aestivum ) can undoubtedly assist in overcoming the bottleneck.…”

Section: Introductionmentioning

confidence: 99%

Identifying and Characterizing Candidate Genes Contributing to a Grain Yield QTL in Wheat

Saieed,

Zhao,

Islam

et al. 2023

Plants

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The current study focuses on identifying the candidate genes of a grain yield QTL from a double haploid population, Westonia × Kauz. The QTL region spans 20 Mbp on the IWGSC whole-genome sequence flank with 90K SNP markers. The IWGSC gene annotation revealed 16 high-confidence genes and 41 low-confidence genes. Bioinformatic approaches, including functional gene annotation, ontology investigation, pathway exploration, and gene network study using publicly available gene expression data, enabled the short-listing of four genes for further confirmation. Complete sequencing of those four genes demonstrated that only two genes are polymorphic between the parental cultivars, which are the ferredoxin-like protein gene and the tetratricopeptide-repeat (TPR) protein gene. The two genes were selected for downstream investigation. Two SNP variations were observed in the exon for both genes, with one SNP resulting in changes in amino acid sequence. qPCR-based gene expression showed that both genes were highly expressed in the high-yielding double haploid lines along with the parental cultivar Westonia. In contrast, their expression was significantly lower in the low-yielding lines in the other parent. It can be concluded that these two genes are the contributing genes to the grain yield QTL.

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“…There is overwhelming evidence supporting that sepsis is a highly heterogeneous disease with large inter-individual differences in the disease course and genetic factors influencing individual vulnerability to, and the severity of, infections ( Frodsham and Hill, 2004 ). For example, the genetic variant rs2737190 is in the promoter region of the TLR4 gene, and the GG genotype produces an improvement in the immune response ( Colin-Castro et al, 2021 ). Another example is that 593C>T GPx1 SNP in sepsis patients leads to high organ dysfunction, sepsis shock, and mortality risk ( Majolo et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

LNC-ZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis

et al. 2022

Front. Genet.

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Background: Sepsis is a severe systemic reaction disease induced by bacteria and virus invading the bloodstream and subsequently causing multiple systemic organ dysfunctions. For example, the kidney may stop producing urine, or the lungs may stop taking in oxygen. Recent studies have shown that long non-coding RNAs (lncRNAs) are related to the dysfunction of organs in sepsis. This study aims to screen and validate the sepsis-associated lncRNAs and their functional single nucleotide polymorphisms (SNPs).Result: Unconditional multiple logistic regression based on the recessive model (adjusted odds ratio = 2.026, 95% CI = 1.156–3.551, p = 0.0136) showed that patients with the CC genotype of rs579501 had increased risk of sepsis. Stratification analysis by age and gender indicated that patients with the rs579501 CC genotype had higher risk of sepsis among children aged <12 months (adjusted odds ratio = 2.638, 95% CI = 1.167–5.960, p = 0.0197) and in male patients (adjusted odds ratio = 2.232, 95% CI = 1.127–4.421, p = 0.0213). We also found a significant relationship between rs579501 and severe sepsis risk (CC versus AA/AC: adjusted odds ratio = 2.466, 95% CI = 1.346–4.517, p = 0.0035). Stratification analysis for prognosis and number of organ dysfunctions demonstrated that the rs579501 CC genotype increased non-survivors’ risk (adjusted odds ratio = 2.827, 95% CI = 1.159–6.898, p = 0.0224) and one to two organs with dysfunction risk (adjusted odds ratio = 2.253, 95% CI = 1.011–5.926, p = 0.0472).Conclusion: Our findings showed that the lnc-ZNF33B-2:1 rs579501 CC genotype increases the susceptibility to sepsis. From the medical perspective, the lnc-ZNF33B-2:1 rs579501 CC genotype could be serving as a biochemical marker for sepsis.

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Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP

Cited by 4 publications

References 64 publications

Monitoring of the Forgotten Immune System during Critical Illness—A Narrative Review

Monitoring of the Forgotten Immune System during Critical Illness—A Narrative Review

Identifying and Characterizing Candidate Genes Contributing to a Grain Yield QTL in Wheat

LNC-ZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis

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