engleski

Platelet glycoprotein polymorphisms in paediatric Cerebral Sinovenous Thrombosis

Objective: Although prothrombotic factors are increasingly recog- nized as an important cause of cerebral sinovenous thrombosis (CSVT) in children, specific platelet glycoprotein (GP) gene polymorphisms have not yet been investigated. Therefore, our aim was to examine the significance of eight polymorphisms, i.e. GPIa C807T and G873A, GPIbI -5T>C, GPVI T13254C and human platelet antigens (HPA) -1, -2, -3 and -5, as well as haplotypes GPIa C807T/G873A/HPA-5, GPIbI -5T>C/HPA-2 and HPA-1/HPA-2/HPA-3, in the paediatric CSVT onset. Methods: The study was part of a project (ID HRZZ IP-2014-09- 2047) and included 20 children (10 boys and 10 girls) with CSVT and 153 sex- and age-matched controls. Genotyping was performed as follows: CVD Strip assay (ViennaLab, Austria) for HPA-1, real-time PCR with TaqMan probes (Ficko T et al., 2004) for HPA-2, -3 and -5, real-time PCR followed by melting curve analysis (Morita H et al., 2001 ; Ulehlova J et al, 2014) for GPIbI -5T>C, GPIa C807T and G873A, and real-time PCR followed by high resolution melting analysis for GPVI T13254C. Results: Among the analyzed single polymorphisms, only the presence of at least one HPA-1b allele was found to be associated with almost 3-fold increased risk for CSVT (OR: 2.73 ; 95% CI: 1.06- 7.04, P=0.040). Moreover, 5-9 fold increased risk for CSVT was identified in carriers of haplotypes HPA-1a/2a/3b (OR: 4.71 ; 95% CI: 1.42-15.64, P=0.012), HPA-1b/2a/3a (OR: 6.71 ; 95% CI: 1.38-32.51, P=0.019) and HPA- 1b/2b/3a (OR: 8.60 ; 95% CI: 1.12-65.89, P=0.040). Conclusion: Our study results reveal HPA-1 as a risk factor for paedi- atric CSVT not only as a single polymorphism, but also as part of three specific HPA-1/HPA-2/HPA-3 haplotypes that increase 2-3 fold the risk for CSVT onset.

Platelet glycoprotein, polymorphisms, paediatric Cerebral Sinovenous Thrombosis

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