title: Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development.
abstract: BACKGROUND
  Nitric oxide (NO) influences susceptibility to infection and hemodynamic failure (HF) in sepsis. NOS3 and NOS2 SNPs might modify plasma nitrite/nitrate (NOx) levels, sepsis development, hemodynamics and survival.
  
  
  METHODS
  90 severely septic and 91 non-infected ICU patients were prospectively studied. NOS3 (E298D), NOS3 (-786 T/C), NOS3 (27 bp-VNTR), and NOS2A (exon 22) SNPs and plasma NOx levels were assessed.
  
  
  RESULTS
  21 patients (11.6%) died, 7 with sepsis. TT homozygotes and T allele carriers of NOS3 (E298D) and AG carriers of the NOS2A (exon 22) SNPs were more frequent among septic compared to non-infected ICU patients (p < 0.05). Plasma NOx was higher in septic, especially in septic with hemodynamic failure (HF) or fatal outcome (p < 0.006). Plasma NOx was higher in carriers of the T allele of the NOS3 (E298D) SNP (p = 0.006). Sepsis independently associated with HF, increased NOx, peripheral neutrophils, and fibrinogen levels, decreased prothrombin and the presence of the NOS3 (E298D) and NOS2A (exon 22) SNPs. A low APACHE II score was the only variable associated with sepsis survival. NOx was independently associated with sepsis, HF, decreased neutrophils and higher APACHE.
  
  
  CONCLUSIONS
  NOS3 (E298D) and NOS2A (exon 22) SNPs, individually and in combination, and plasma NOx, associated with sepsis development. NOx associated with HF and fatal outcome.
authors.affiliation: Critical Care, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Martin
authors.affiliation: Infectious Diseases Services, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain. Electronic address: vasensia@gmail.com.
authors.forename: Víctor
authors.initials: V
authors.lastname: Asensi
authors.affiliation: Biochemistry and Molecular Biology, Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: A Hugo
authors.initials: AH
authors.lastname: Montes
authors.affiliation: Infectious Diseases Unit, Hospital de Galdácano, Vizcaya, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Collazos
authors.affiliation: Molecular Genetics Unit-Nephrology Research Institute, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.affiliation: Biochemistry and Molecular Biology, Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Is
authors.affiliation: Infectious Diseases Services, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Carton
authors.affiliation: Critical Care, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Taboada
authors.affiliation: Biochemistry and Molecular Biology, Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valle-Garay
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D018805:Sepsis / Q000097:blood* / Q000201:enzymology
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Hemodynamic failure; Nitric oxide; Nitric oxide synthase; Polymorphisms; Sepsis; Survival