Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis

Jabandžiev, Petr; Šmerek, Michal; Michálek, Jaroslav; Fedora, Michal; Kosinová, Lucie; Hubacek, Jaroslav A.

doi:10.1186/cc13174

Cited by 41 publications

(39 citation statements)

References 39 publications

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“…The majority of previous studies related to SNPs in sepsis were performed on adults [36]. However, data from neonate populations with sepsis are poor, and developmental differences that affect inflammation and immune responses make it difficult to extrapolate data from adult studies to newborn populations [8,48]. The current study focused on analyses of SNPs in four genes (IL-1β 65-5.38), p value = 0.004) -31 T/C, IL-6 -174 G/C, TNF-α -308 G/A, and IFN-γ +874 A/T) that may play a critical role in, or are associated with, inflammatory response and sepsis severity, in order to identify possible predictive mechanisms for sepsis risk stratification.…”

Section: Discussionmentioning

confidence: 99%

Clinical immunology Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

Allam¹,

Alsulaimani²,

Alzaharani³

2015

cejoi

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In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.

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Section: Discussionmentioning

confidence: 99%

Clinical immunology Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

Allam¹,

Alsulaimani²,

Alzaharani³

2015

cejoi

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“…Despite previous studies have indicated genetic variants combined and/or into the traditional risk model could enhance the discriminatory capacity. For example, Jabandziev et al [33] demonstrated specific combinations of five polymorphisms in the BPI (rs5743507), LBP (rs2232618), TLR4 (rs4986790), HSP70 (rs2227956), and IL-6 (rs1800795) genes appeared to predict outcome of life-threatening sepsis in children. Shimada's study [34] indicated the combined panel of TNFA − 308G/A and IL1B -31C/T plus APACHE II score might enable more accurate prediction of outcome in septic patients.…”

Section: Discussionmentioning

confidence: 99%

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

Wen

Sun

et al. 2020

Preprint

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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 used 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 traumatic sepsis (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 (P trend =6.81×10 -8 ), higher SOFA (P trend =5.00×10 -3 ) and APACHEII score (P trend =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 predictors could improve the predictive ability of risk model for sepsis and highlighted the application among trauma populations, indicating that the sepsis risk assessment model will be a promising tool for high risk population screening and prediction.

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“…Despite previous studies have indicated genetic variants combined and/or into the traditional risk model could enhance the discriminatory capacity. For example, Jabandziev et al [33] demonstrated speci c combinations of ve polymorphisms in the BPI (rs5743507), LBP (rs2232618), TLR4 (rs4986790), HSP70 (rs2227956), and IL-6 (rs1800795) genes appeared to predict outcome of life-threatening sepsis in children. Shimada's study [34] indicated the combined panel of TNFA − 308G/A and IL1B -31C/T plus APACHE II score might enable more accurate prediction of outcome in septic patients.…”

Section: Discussionmentioning

confidence: 99%

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

Wen

Sun

et al. 2020

Preprint

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.

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Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis

Cited by 41 publications

References 39 publications

Clinical immunology Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

Clinical immunology Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms

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

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

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