title: Clinical associations of host genetic variations in the genes of cytokines in critically ill patients.
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.
authors.affiliation: N. I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: O B
authors.initials: OB
authors.lastname: Belopolskaya
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences.
authors.forename: T V
authors.initials: TV
authors.lastname: Smelaya
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences.
authors.forename: V V
authors.initials: VV
authors.lastname: Moroz
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences.
authors.forename: A M
authors.initials: AM
authors.lastname: Golubev
authors.affiliation: N. I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.|V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences.
authors.forename: L E
authors.initials: LE
authors.lastname: Salnikova
mesh_terms: D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D016638:Critical Illness; D016207:Cytokines / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000401:mortality; D018805:Sepsis / Q000235:genetics / Q000401:mortality; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: adult respiratory distress sybdrome; cytokines; genetic association studies; sepsis; single nucleotide polymorphism