Interleukin-6 gene variants and the risk of sepsis development in children

Michálek, Jaroslav; Svetlikova, Petra; Fedora, Michal; Klimovič, Michal; Klapačová, Lenka; Bartošová, Drahomíra; Hrstková, Hana; Hubacek, Jaroslav A.

doi:10.1016/j.humimm.2007.06.003

Cited by 47 publications

(49 citation statements)

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“…[19,20] Recent studies have identifi ed that IL-6 -174G/C and -572G/C, bactericidal permeability increasing (BPI) protein gene Taq polymorphism, human β-defensin 1 gene (DEFB1) -44G/C, and protein C-1641AA genotype as well as IL-1 receptor-associated kinase (IRAK-1) haplotype were associated with the Haplotypes Control subjects (n=152) Septic shock patients (n=124) P value Surviving patients (n=55) Non-surviving patients (n=69) P value AA 77. 16 Table 7. Haplotype analysis of rs2234237and rs2234246 in patients with septic shock and control subjects and in the survivors and non-survivors clinical course of severe sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Haplotype analysis of rs2234237and rs2234246 in patients with septic shock and control subjects and in the survivors and non-survivors clinical course of severe sepsis. [16][17][18][19][20] It is anticipated that these fi ndings will lead to the use of new diagnostic markers, prognostic indicators, and therapeutic strategies for sepsis. [29] In this study, two common SNPs in the TREM-1 gene were evaluated with regard to the susceptibility and prognosis of septic shock.…”

Section: Discussionmentioning

confidence: 99%

“…Studies [16][17][18][19][20] confirmed that single nucleotide polymorphisms (SNPs) in some particular genes, such as interleukin-6 gene polymorphisms G-174>C and G-572>C, bactericidal permeability increasing protein (BPI) (G545>C) Taq and BPI (A645>G) 216, β-defensin 1 variant haplotype -20G/-44G/-52G, IRAK-1 variant haplotype, protein C-1641 AA genotype, etc, play a critical role in severe sepsis or septic shock.…”

Section: Introductionmentioning

confidence: 98%

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Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

Peng¹,

Li²,

Zhou³

et al. 2015

World Journal of Emergency Medicine

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BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock. METHODS:We genotyped two TREM-1 single nucleotide polymorphisms (SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model (AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model (AG, OR=0.72, 95%CI 0.43-1.19, P=0.02; AA, OR=2.71, 95%CI 1.00-7.42; P=0.03). However, in three inherited models (dominant model, recessive model, and codominant model), none of the assayed loci was signifi cantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels (99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/mL, AG 85.4±43 pg/mL, and GG 65.3±30.7 pg/mL (P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes (P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

Peng¹,

Li²,

Zhou³

et al. 2015

World Journal of Emergency Medicine

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“…Michalek recorded that elevated IL6 level was detected in septic patients and the G allele could be associated with increased levels of plasma IL6 [11]. Schlüter also found that the median systemic IL6 levels in septic patients were markedly elevated but were not associated with the IL6 promoter genotype [5].…”

Section: Discussionmentioning

confidence: 98%

“…Zidan et al, [16] observed an association between homozygous IL6-174 GG and protection against severe sepsis complications, where GG and GC patients suffered severe sepsis by9.5% and 20%, respectively [16]. Michalek et al [11] were able to demonstrate that homozygous CC variant at position-174 of the IL6 gene seemed to be associated with septic shock and that the variant in the IL6 gene played an important role in children with sepsis. He also concluded that, C/C genotype in a general Caucasian population is probably less protective against serious conditions leading to sepsis [11].…”

Section: Discussionmentioning

confidence: 99%

IL6-174 G/C Gene Polymorphism in Children with Septicemia: Single Center Study

Shahin¹

2016

JPNC

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Background: Sepsis represents the main cause of mortality at intensive care units, with mortality rates from 30-50%. Elderly, pediatric, and immunecompromised patients show atypical clinical manifestations of bacterial infection. Several studies showed that Cytokines are involved in the pathogenesis of sepsis. We conducted this study to investigate the association of IL6-174 G/C gene polymorphism with sepsis outcome in critically ill children admitted to pediatric intensive care units. Patients and methods:Sixty children were included, thirty cases with sepsis and septic shock admitted to pediatric ICU in children's hospital Cairo University. Their ages ranged from 2 months to 24 months (2 years), with 18 (60%) males and 12 (40%) females in comparison to 30 healthy controls. Blood samples (5 ml) were collected (2 ml. on EDTA for DNA extraction and RFLP of IL-6 gene at locus 174. The rest was used for separation of serum for determination of IL-6 protein by ELISA technique.Results: IL6 serum levels were significantly elevated in those children with septicemia and septic shock (114 pg/ml) compared to healthy matched controls (2.60 pg/ml), p <0.001. Regarding the IL6-174 genotype; G/C, G/G and CC represents 53.3%, 36.7% and 10%, respectively. Comparing the genotypes with mortality rates for those children with sepsis and septic shock, IL6-174, GC, GG and CC were 46.7%, 66.3%, and 100% respectively. Conclusion:IL6 serum levels are elevated in patients with sepsis, supporting its role in the pathogenesis of sepsis. IL6-174 G/C gene polymorphism may contribute to the prognosis and outcome of sepsis.Recommendation: Further large-scale studies are needed to clarify the role of IL6-174 genotypes in association with critical illnesses in children. Using IL-6 polymorphisms as a routine test in patients admitted to PICU may help us predict the prognosis of critically ill children, and allow for better treatment options for those who are at risk.

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Genetic Polymorphisms in Critical Illness and Injury

Dahmer

Quasney

2014

Pediatric Critical Care Medicine

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Interleukin-6 gene variants and the risk of sepsis development in children

Cited by 47 publications

References 21 publications

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

IL6-174 G/C Gene Polymorphism in Children with Septicemia: Single Center Study

Genetic Polymorphisms in Critical Illness and Injury

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