engleski

Association of Glycoprotein Ia Gene Polymorphisms with Pediatric Ischemic Stroke

Background: Genetic risk factors for ischemic stroke (IS) in children are still incompletely characterized. Recent meta-analysis that included polymorphisms in glycoprotein Ia (GPIa) gene: dimorphism C807T and G873A, and human platelet antigen (HPA) -5, confirmed association of GPIa 807T allele with increased risk for ischemic stroke in Asian adults (Liu H et al., 2017), but studies including children are lacking. Aims: To study the association of individual polymorphisms HPA-5, GPIa C807T and G873A and their haplotypes with pediatric IS and its subtypes: arterial IS (AIS), including perinatal (PAIS) and childhood AIS (CAIS), and cerebral sinovenous thrombosis (CSVT). Methods: The study group comprised 157 children with a confirmed diagnosis of IS (68 with PAIS, 70 with CAIS and 19 with CSVT) and 153 age- and sex-matched healthy children as a control group. Genotyping of HPA-5 was performed using real-time PCR with TaqMan probes (Ficko T et al., 2004). Genotyping of GPIa C807T and G873A was performed using real-time PCR followed by melting curve analysis (Morita H et al., 2001). The study was part of a project funded by Croatian Science Foundation (IP-2014-09-2047). Results: The investigation of individual polymorphisms revealed that the presence of at least one HPA-5b allele was associated with a lower risk of IS (OR:0.59, 95% CI:0.31-1.10) but the difference was not statistically significant (P=0.096) ; however, a significant association was found for CAIS (OR:0.39, 95% CI:0.15-1.00) but not for PAIS (OR:0.83, 95% CI:0.38-1.79), or SVT (OR:0.51, 95% CI:0.11- 2.34). Although lower but nonsignificant bCG haplotype (HPA-5/GPIa C807T/GPIa G873A) frequency (P=0.068) was calculated for IS (0.066) compared to controls (0.101), a 2.5-fold lower risk for CAIS (OR:0.37 ; 95% CI:0.14-0.93) was identified for the same haplotype carriers. Conclusions: The obtained results suggest that a new, previously unreported single polymorphysm HPA-5 in GPIa is, together with the haplotype (HPA-5/GPIa C807T/GPIa G873A), protective against CAIS.

paediatric ischemic stroke ; glycoprotein ; polymorphism

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