title: Endothelial nitric oxide synthase G894T (GLU298ASP) polymorphism is associated with hypotension in patients with E. coli bacteremia but not in bacteremia caused by a gram-positive organism.
abstract: Nitric oxide (NO) as a vasoactive substance is a crucial element in the pathogenesis of sepsis. Endothelial NO synthase (eNOS) is, in turn, a key regulator of vascular NO production. The eNOS gene polymorphism at position 894 (G>T, Glu298Asp) resulting in T allele has been studied in the context of vascular diseases, but its role in sepsis has not yet been explored. We here studied the effect of eNOS Glu298Asp polymorphism on the clinical course of the disease in patients with bacteremia. The study comprised 147 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci, or Escherichia coli. Laboratory findings and clinical data were registered on admission and during 6 consecutive days. The polymorphism of eNOS gene, G894T, was genotyped. Carriage of the T allele was associated with low MAP (P = 0.004) and high Sequential Organ Failure Assessment score (P = 0.001) in patients with E. coli bacteremia. The effect on blood pressure was most prominent in the early stage of the disease (MAP on admission = 52 mmHg in T-allele carriers vs. 91 mmHg in noncarriers; P < 0.001). However, the same was not detected in bacteremia caused by a gram-positive organism (S. aureus, S. pneumoniae, or beta-hemolytic streptococci). The Glu298Asp polymorphism had no effect on case fatality in any pathogen. Carriage of the T allele of the eNOS gene is a risk factor for hypotension in patients with E. coli bacteremia but not in bacteremia caused by a gram-positive organism.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. Reetta.Huttunen@uta.fi
authors.forename: Reetta
authors.initials: R
authors.lastname: Huttunen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Janne
authors.initials: J
authors.lastname: Laine
authors.forename: Carita
authors.initials: C
authors.lastname: Eklund
authors.forename: Risto
authors.initials: R
authors.lastname: Vuento
authors.forename: Janne
authors.initials: J
authors.lastname: Aittoniemi
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Jaana
authors.initials: J
authors.lastname: Syrjänen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000150:complications / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000502:physiology; D016908:Gram-Positive Bacterial Infections / Q000150:complications*; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D052250:Nitric Oxide Synthase Type III