title: Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection.
abstract: BACKGROUND
  Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection.
  
  
  METHODS
  Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped.
  
  
  RESULTS
  The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102-1041 vs. median 175, range 51-1499 μmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3-14 vs. median 6, range 2-15 days; p = 0.032). The rare A-allele carriers (i.e. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74-170 vs.116, range 86-162 mmHg, p = 0.019, and median 68, range 40-90 vs. 72, range 48-100 mmHg; p = 0.003, respectively).
  
  
  CONCLUSIONS
  Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Koskela
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.|School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Laine
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.|School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.|Science Centre, Pirkanmaa Hospital District, Tampere, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pessi
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.|Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Tuomisto
authors.affiliation: School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.|Fimlab Laboratories Ltd, Tampere, Finland.
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.|School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.|School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005838:Genotype; D018778:Hantavirus Infections / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006720:Homozygote; D006760:Hospitalization; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D029262:Puumala virus; D055815:Young Adult
chemical_list: C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III