Patients with IL-10 (-1082A/A) genotypes were found significantly higher in post traumatic sepsis patients and had a significantly higher risk to developed sepsis complication (p < 0.05, OR = 0.86, C.I = 0.08-8.8).In case of TNF-α (-308) position, GA and GG genotype patients have a significantly lower risk of poor outcome (p < 0.05, OR = 0.25, C.I = 0.01-1.3) and (p < 0.05, OR = 0.22, C.I = 0.01-0.5) in comparison to AA genotype.
Combined with our previous in vitro functional study, the results suggest that the TLR4 11367 polymorphism might be a good predictor of who is more likely to develop complications such as sepsis or multiple organ dysfunction syndrome, depending on genotype.
Specific point mutations in the human toll-like receptor 4 (TLR4) confer altered risk for diverse diseases including sepsis, aspergillosis and inflammatory bowel disease.
Animal studies suggest that aPC variants with near-normal signaling function, but with greatly diminished anticoagulant potential may exhibit a substantially improved risk-to-benefit ratio in sepsis therapy.
The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis.
Serum levels of tumour necrosis factor, interleukin (IL)-10, and IL-6 at sepsis onset did not significantly differ between patients carrying wild-type and mutant TLR4.
Our study investigated the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis.
<b>Conclusion</b> We uncovered an association between IL-10 1082 gene variation and sepsis in VLBW infants but did not identify associations between neonatal sepsis and TNF-α 308 or IL-6 gene variation.
While the genotype TNF-beta1/beta2 has a higher risk for developing complications in general, the TNF-beta2/beta2 genotype is associated with more severe complications and mortality from sepsis.
Candidate genes for asthma and allergic diseases co-associated with sepsis including innate immunity receptors and related molecules (CD14, TLR4 and AOAH) and novel genes such as MYLK provide good examples of pleitropic effects of innate immunity genes, where variants conferring risk to specific traits (i.e. sepsis) under one set of genetic and environmental circumstances confer a reduced risk in a different (but possibly related) clinical outcome (i.e. allergic asthma), and support the 'common variant/multiple disease' hypothesis.
Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006).
Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections.
We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis.
This study evaluates the relationship between polymorphisms in the first intron of the interferon-gamma gene and the development of sepsis after trauma.
In this study, the relationship between the TNF-alpha308G/A, the IL-6-174 G/C, the PAI-1, the FVL, the EPCR, and the Cathepsin G (Ars 125 Ser) polymorphisms and the development and outcome of sepsis in pediatric patients was studied.
The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520).