Innate Immunity SNPs are Associated with Risk for Severe Sepsis after Burn Injury

Barber, Robert C.; Chang, Ling Yu; Arnoldo, Brett D.; Purdue, Gary F.; Hunt, John L.; Horton, Jureta W.; Aragaki, Corinne

doi:10.3121/cmr.4.4.250

Cited by 92 publications

(58 citation statements)

References 44 publications

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“…Human studies have demonstrated an association of these variants with susceptibility to gram negative bacterial infections and septic shock [22][23][24] and mortality in patients with systemic inflammatory response syndrome [25]. In addition, a TLR4 polymorphism was found to be associated with an increased risk of severe sepsis in adult burn patients [26]. However, not all studies have confirmed this finding [27,28], nor does the variant appear to be associated with either susceptibility to, or severity of, meningococcal disease specifically [29].…”

Section: Toll-like Receptorsmentioning

confidence: 61%

“…For example, among adults with septic shock, the frequency of the less common A allele at the TNF--308 position is higher in those who died, and the risk of death was 3.7-fold greater in those patients with at least one copy of the TNF--308A allele even after controlling for age and severity of illness [94]. Other studies demonstrating an association of "high-secretor" genotypes and more severe disease include children with meningococcal infections [95] and bacteremia [90], severe sepsis in adults [26,83,85,96], and community acquired pneumonia in adults [97,98]. However, these results have not been uniformly observed [28,[99][100][101][102][103], and further studies are needed.…”

Section: Tumor Necrosis Factor (Tnf-)mentioning

confidence: 99%

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Host Genetics and Pediatric Sepsis

Quasney¹

2011

TOINFJ

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Susceptibility to, and outcome from, sepsis in children is highly variable due in part to genetic variation in genes coding for components of the innate immune response. This review article will discuss evidence for the influence of host genetic variability on the susceptibility to, and outcome from, sepsis in children and adults. Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (TLR4, CD-14, Fc RIIa, and mannose binding lectin) and the response to bacterial pathogens (TNF-, IL-1 , IL-1 , IL-1 RA , IL-6, IL-10, heat shock proteins, ACE, plasminogen activator inhibitor-1) can influence the amount or function of the protein produced in response to bacterial stimuli. Evidence is discussed suggesting that some of these genetic polymorphisms influence the susceptibility to, and outcome from, sepsis. Conclusion:Host genetic variability in the regulatory and coding regions of genes for components of the innate immune system may influence the susceptibility to and/or outcome from sepsis. The disparate results observed in many studies of polymorphisms in sepsis emphasize the need for future studies to be larger, to include the analysis of multiple polymorphisms, and to be better designed with respect to control populations in order to identify the degree of influence that genetic variability has on sepsis.

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Section: Toll-like Receptorsmentioning

confidence: 61%

Section: Tumor Necrosis Factor (Tnf-)mentioning

confidence: 99%

Host Genetics and Pediatric Sepsis

Quasney¹

2011

TOINFJ

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“…It was found that risk of severe sepsis after burn injury had an association with 299Gly [59]. In the case of systemic inflammatory response syndrome (SIRS), 299Gly was found to be associated with increased mortality rate [60].…”

Section: Sepsismentioning

confidence: 93%

TLR4 polymorphisms and disease susceptibility

et al. 2012

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Toll-like receptors (TLRs) play a central role in the regulation of the host immune system. Each TLR recognizes specific pathogen-associated molecular patterns (PAMPs). TLR4 is one of the well characterized pathogen recognition receptors (PRRs) that recognizes the lipopolysaccharide (LPS) of Gram-negative bacteria, some conserved structures from fungal to mycobacterial pathogens and some endogenous ligands. A complex signaling cascade initiates after the ligand binds to the TLR4 ectodomain, leading to the activation of multiple inflammatory genes. Genetic variations greatly influence immune responses towards pathogenic challenges and disease outcome. In this review, we summarize various reports regarding TLR4 polymorphisms and disease susceptibility.

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“…after adjustment for age, ethnicity, gender, burn size and inhalation injury, variant alleles at tnF-α 308A, TLR4, IL-6 and CD14 were significantly associated with an increased risk for severe sepsis (54).…”

Section: Tnf-β Genotype ---------------------------------------------mentioning

confidence: 99%

Association of tumor necrosis factor β genetic polymorphism and sepsis susceptibility

Delongui

Grion

Watanabe

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. the association of the tumor necrosis factor β (tnF-β) nco1 genetic polymorphism with susceptibility to sepsis was evaluated in 60 consecutive patients diagnosed with sepsis and in 148 healthy blood donors. Genomic dna was extracted from peripheral blood cells and a 782 base-pair fragment of the tnF-β gene was amplified by PCR. The pcr products were subjected to nco1 restriction digestion and analysed by restriction fragment length polymorphism analysis. tumor necrosis factor α (tnF-α) and the c-reactive protein (crp) serum levels were also determined by EliSa and nephelometry, respectively. among the septic patients, the allelic frequencies of tnFB1 and tnFB2 were 0.2833 and 0.7166, respectively, and they differed from those observed in the blood donors (p=0.0282). the tnFB2 allele frequency was higher in the septic patients than in the blood donors [odds ratio=1.65 (ci 95% 1.02-2.69), p=0.0315]. the tnF-α and crp serum levels and the apachE ii and SOFa clinical scores did not differ in the patients with the tnFB1 or tnFB2 alleles (p>0.05). the results suggest that the tnFB2 allele is associated with susceptibility to sepsis, but it was not found to be associated with the immunological and clinical biomarkers of the disease.

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Innate Immunity SNPs are Associated with Risk for Severe Sepsis after Burn Injury

Cited by 92 publications

References 44 publications

Host Genetics and Pediatric Sepsis

Host Genetics and Pediatric Sepsis

TLR4 polymorphisms and disease susceptibility

Association of tumor necrosis factor β genetic polymorphism and sepsis susceptibility

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