ABSTRACT
Host 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 -511A and IL8 -251A) and mortality (IL1B -511A). 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 anti-inflammatory cytokines may contribute to different clinical phenotypes in patients at high risk of critical illness.
Subject(s)
Critical Illness , Cytokines/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , Adult , Biomarkers , Case-Control Studies , Female , Genotype , Humans , Intensive Care Units , Male , Middle Aged , Odds Ratio , Prognosis , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/mortality , Sepsis/genetics , Sepsis/mortality , Young AdultABSTRACT
This study presents the results of research on DNA polymorphism in children with malignant brain tumors (172 patients, 183 in the control group). Genotyping was performed using an allele-specific tetraprimer reaction for the genes of the first (CYP1A1 (2 sites)) and second phases of xenobiotic detoxication (GSTM1, GSTT1, GSTP1, GSTM3), DNA repair genesXRCC1, XPD(2 sites),OGG1, as well asNOS1andMTHFR.The increased risk of disease is associated with a minor variant ofCYP1A1(606G) (p = 0.009; OR = 1.50) and a deletion variant ofGSTT1, (p = 0.013, OR = 1.96). Maximum disease risk was observed in carriers of double deletions inGSTT1-GSTM1(p = 0.017, OR = 2.42). The obtained results are discussed in reference to literary data on the risk of malignant brain tumor formation in children and adults.
