Clinical associations of host genetic variations in the genes of cytokines in critically ill patients

Abstract

SummaryHost genetic variations may influence a changing profile of biochemical markers and outcome in patients with trauma/injury. The objective of this study was to assess clinical associations of single nucleotide polymorphisms (SNPs) in the genes of cytokines in critically ill patients. A total of 430 patients were genotyped for SNPs in the genes of pro-(IL1B, IL6, IL8) and anti-inflammatory (IL4, IL10, IL13) cytokines. The main end-points were sepsis, mortality and adult respiratory distress syndrome (ARDS). We evaluated the dynamic levels of bilirubin, blood urea nitrogen, creatine kinase, creatinine and lactate dehydrogenase in five points of measurements (between 1 and 14 days after admission) and correlated them with SNPs. High-producing alleles of proinflammatory cytokines protected patients against sepsis (IL1B 2511A and IL8 -251A) and mortality (IL1B 2511A). High-producing alleles of anti-inflammatory cytokines IL4 -589T and IL13 431A (144Gln) were less frequent in ARDS patients. The carriers of IL6 -174C/C genotypes were prone to the increased levels of biochemical markers and acute kidney and liver insufficiency. Genotype-dependent differences in the levels of biochemical indicators gradually increased to a maximal value on the 14th day after admission. These findings suggest that genetic variability in pro-and antiinflammatory cytokines may contribute to different clinical phenotypes in patients at high risk of critical illness.

Developing the nomogram for the prediction of in-hospital incidence of acute respiratory distress syndrome in patients with COVID-19

“…The levels of LDH and CK signi cantly increased in patients with ARDS. LDH and CK were not only markers of in ammation but also indicators of prognosis in critical illness (22,23). Liu(24) et al reported that the patients with acute lung injury also had elevated levels of enzymes including LDH and CK due to in ammation and oxidative stress.…”

MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients

“…In the next step, RNAse III endonuclease, also called Drosha, activates the pri-microRNAs. This reaction is catalyzed by the DiGeorge Syndrome Critical Region 8 (DGCR8) complex, which leads to the formation of pre-microRNAs [15,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74].…”

Clinical Assays in Sepsis: Prognosis, Diagnosis, Outcomes, and the Genetic Basis of Sepsis

“…Results until now have shown association of the allele with higher plasma IL-8 levels, as well as with survival [194]. The A allele has been suggested to be associated with protection against sepsis [195], and also with increased risk of sepsis [196]. The heterozygote AT genotype has been associated with increased risk of developing severe sepsis [197].…”

“…Toll-like receptors (TLRs) -D299G allele of TLR4 gene associated with increased susceptibility to severe bacterial infections and Gram-negative sepsis [192,193] IL-8 -The 251A/T allele has been associated with survival [194], protection against sepsis [195], and also increased risk of sepsis [196] -The heterozygote AT genotype has been associated with increased risk of developing sepsis [197] -Male T allele carriers are more susceptible to sepsis [198] TNF-α -G-to-A polymorphism associated with sepsis [201] -G-to-A polymorphism associated with adverse outcomes in patients with severe sepsis and septic shock [199,200] -No association of G-to-A polymorphism and development of sepsis [202,203] -G-to-A polymorphism not associated with sepsis mortality [201] IL-6 -174 G/C polymorphism showed modest association with neonatal sepsis [209] -174 G/C polymorphism was associated with improved survival rates in patients with sepsis [207] -174 G/C polymorphism was not associated with a difference in survival [208] Angiotensin-converting enzyme (ACE)…”