title: Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection.
abstract: BACKGROUND
  Puumala virus (PUUV) infection is a viral hemorrhagic fever with renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of renal function. We aimed to assess whether genetic polymorphisms of platelet antigens together with those of von Willebrand factor (VWF) and plasminogen activator inhibitor (PAI-1) correlate with disease severity. Patients and methods 172 consecutive hospital-treated patients with serologically confirmed acute PUUV infection were included. Platelet glycoprotein (GP) IIIa T>C (rs5918), GP Ia T>C (rs1126643), GP Ib C>T (rs6065), GP VI T>C (rs1613662), VWF A>G (rs1063856) and PAI-1 A>G (rs2227631) were genotyped. The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed.
  
  
  RESULTS
  PAI-1G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 μmol/l, range 60-1499 μmol/l vs. median 122 μmol/l, range 51-1156 μmol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 μmol/l, 204 μmol/l and 122 μmol/l, respectively, p = 0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels during PUUV infection. The minor C-allele of GP Ia associated with lower platelet counts (median 44 × 10(9)/l, range 20-90 × 10(9)/l vs median 64 × 10(9)/l, range 3-238 × 10(9)/l; p = 0.02).
  
  
  CONCLUSIONS
  Polymorphism of PAI-1, a major regulator of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV-HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower platelet count.
authors: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. outi.k.laine@fimnet.fi
authors: Outi
authors: O
authors: Laine
authors: Lotta
authors: L
authors: Joutsi-Korhonen
authors: Satu
authors: S
authors: Mäkelä
authors: Jussi
authors: J
authors: Mikkelsson
authors: Tanja
authors: T
authors: Pessi
authors: Sari
authors: S
authors: Tuomisto
authors: Heini
authors: H
authors: Huhtala
authors: Daniel
authors: D
authors: Libraty
authors: Antti
authors: A
authors: Vaheri
authors: Pekka
authors: P
authors: Karhunen
authors: Jukka
authors: J
authors: Mustonen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005838:Genotype; D018778:Hantavirus Infections / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D007668:Kidney / Q000503:physiopathology*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D029262:Puumala virus; D013921:Thrombocytopenia / Q000097:blood / Q000503:physiopathology / Q000821:virology*; D055815:Young Adult
chemical_list: D039421:Integrin alpha2; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human