engleski

Significance of GPIbα -5T>C, GPIbα VNTR, GPVI T13254C polymorphisms and HPA-2 in the etiology of pediatric arterial ischemic stroke

Background: The etiology of pediatric arterial ischemic stroke (AIS) has still not been fully elucidated. The role of platelet glycoprotein (GP) Ibα polymorphisms: -5T>C, variable number of tandem repeats (VNTR) and human platelet antigen (HPA) -2, which was found to be relevant for the expression and function of GPIbα, has been investigated and associated with increased risk for stroke in adults only. The minor GPVI T13254C allele has been associated with decreased platelet activation. To date, significance of these polymorphisms in pediatric AIS has not been examined. Aim: To investigate the significance of individual polymorphisms GPIbα -5T>C and VNTR, HPA-2 and GPVI T13254C, together with the haplotype (HPA- 1/-2/-3 and GPIbα -5T>C) in pediatric AIS and its subtypes, perinatal and childhood AIS. Methods: Polymorphisms were investigated in 123 children with perinatal (N=58) and childhood AIS (N=65), and in 113 sex- and age- matched controls. Genotyping was performed as follows: GPIbα -5T>C by real-time PCR and melting curve analysis (Ulehlova et al, 2014), GPIbα VNTR using PCR followed by PCR product analysis by electrophoresis on 2% agarose gel (Jilma- Stohlawetz et al, 2003), HPA-1, -2 and -3 by real- time PCR using TaqMan technology (Ficko et al, 2004) and GPVI T13254C using real-time PCR followed by high resolution melting analysis. Results: Increased risk for childhood AIS was found in carriers of VNTR B allele (OR:2.22 ; 95% CI:1.14-4.32). Statistically significantly (P=0.030) higher HPA-1a/2b/3a/GPIbα -5T haplotype frequency (0.099) was observed in AIS, compared to controls (0.026), resulting in OR of 3.60 (95% CI:1.14-11.35). This association was even stronger in children with childhood AIS (OR:5.48 ; 95% CI:1.62-18.49), but not present in children with perinatal AIS (P=0.960). Conclusions: The obtained results show that GPIbα polymorphisms increase the risk solely for childhood AIS, whereas their role does not seem to be important in the etiology of perinatal AIS.

pediatric stroke, polymorphisms, glycoprotein Ibα, human platelet antigen

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