Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Introduction: 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-1 G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 mu mol/l, range 60-1499 mu mol/l vs. median 122 mu mol/l l, range 51-1156 mu mol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 mu mol/l, 204 mu mol/l and 122 mu mol/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 44x10(9)/l, range 20-90 x 10(9)/l vs median 64 x 10(9)/l, range 3-238 x 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. (c) 2011 Elsevier Ltd. All rights reserved.