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

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• 作者：Outi Laine^a ; ^{outi.k.laine@fimnet.fi} ; Lotta Joutsi-Korhonen^b ; Satu Mä ; kelä ; ^a ; Jussi Mikkelsson^c ; Tanja Pessi^d ; ^e ; Sari Tuomisto^d ; ^e ; Heini Huhtala^f ; Daniel Libraty^g ; Antti Vaheri^h ; Pekka Karhunen^d ; ^e ; Jukka Mustonen^a ; ^d
• 关键词：PUUV ; Puumala virus ; HFRS ; hemorrhagic fever with renal syndrome ; VWF ; von Willebrand factor ; PAI ; plasminogen activator inhibitor ; GP ; glycoprotein ; NE ; nephropathia epidemica ; HLA ; human leukocyte antigen ; HPA ; human platelet alloantigen ; CBC ; complete
• 刊名：Thrombosis Research
• 出版年：2012
• 期刊代码：247_00493848
• 类别：med
• 出版时间：May, 2012
• 卷：129
• 期：5
• 页码：611-615
• 文件大小：220 K

摘要

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 渭mol/l, range 60-1499 渭mol/l vs. median 122 渭mol/l, range 51-1156 渭mol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 渭mol/l, 204 渭mol/l and 122 渭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 44 脳 10⁹/l, range 20-90 脳 10⁹/l vs median 64 脳 10⁹/l, range 3-238 脳 10⁹/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.