engleski

Human Platelet Alloantigens and P-Selectin Gene Polymorphisms in Pediatric Arterial Ischemic Stroke

Background: Pediatric arterial ischemic stroke (AIS) is a heterogenous multifactorial disorder, with a wide range of identified inherited and acquired risk factors. Genetic risk factors are incompletely characterized with only FV Leiden being consistently associated with pediatric AIS. We have also demonstrated that inherited genetic risk factors for perinatal and childhood AIS are not the same (Coen Herak et al in press). Aims: The study aimed to find out if individual gene polymorphisms or haplotypes of: a) human platelet alloantigens (HPA) and b) P-selectin (P-SEL) gene alone and combined with FV Leiden are risk factors for perinatal and childhood AIS. Methods: Study group comprised 110 children with childhood (N=61) and perinatal AIS (N=49), and 100 age- and sex-matched controls. Genotyping of HPA-1, -2, -3 and P-SEL-S290N, -N562D, V599L, -T715P were preformed using allele-specific PCR. Results: Carriers of at least one HPA-3b allele had a 2-fold lower risk of AIS (OR: 0.48, 95% CI: 0.26-0.89, P=0.018) and perinatal AIS (OR: 0.45, 95% CI: 0.21-0.97, P=0.041), but not of childhood AIS (P=0.075). Increased risk for AIS was not found for any single P-SEL gene polymorphism, but carriers of PSEL-562DD genotype had a 2.37-fold (95% CI: 1.07-5.23, P=0.034) increased risk for perinatal AIS. The presence of P-SEL-599LL genotype was significantly associated with childhood AIS (P=0.048). Haplotype ANDVT (FV Leiden/P-SEL-S290N/N562D/V599L/T715P) was identified more frequently in perinatal AIS (0.053) compared to controls (0.005), but the difference was not statistically significant (P=0.075). On contrary, lower, although nonsignificant HPA-1a/2a/3b haplotype frequency (P=0.078) was found in childhood AIS (0.242) compared to controls (0.365). Conclusions: Identified association of HPA-3b allele with perinatal AIS and different P-SEL polymorphisms with perinatal and childhood AIS corroborate our previous finding that perinatal and childhood AIS do not share the same genetic risk factors.

HPA ; P-selectin ; pediatric ; AIS ; polymorphism

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