Are inherited prothrombotic gene polymorphisms associated with lesion location in pediatric arterial ischemic stroke?

Pediatric arterial ischemic stroke (AIS) is a relatively rare disorder with multifactorial etiology. A variety of incompletely investigated genetic polymorphisms may cause hypercoagulability and lead to ischemic lesion formation in different parts of brain. As correlation between neuroimaging finding and genetic risk factors might be helpful for further therapeutic decisions, we investigated the significance of inherited prothrombotic gene polymorphisms in different pediatric AIS subtypes according to time of onset and lesion location. Eleven polymorphisms (FV Leiden, FV HR2, FII G20210A, β-fibrinogen −455G>A, FXIII-A Val34Leu, PAI-1 4G/5G, HPA-1, MTHFR C677T, MTHFR A1298C, ACE I/D, apoE ε2-4) were genotyped using a multilocus CVD Strip assay (ViennaLab, Austria) in DNA extracted from blood samples of 112 children (46 girls, 66 boys) with perinatal (N = 51) and childhood AIS (N = 61), and 110 sex- and age-matched controls. FV Leiden (OR: 4.24 ; 95% CI: 1.16–15.46, p = 0.015) and ACE I/D (OR: 1.90 ; 95% CI: 1.01–3.55, p = 0.044) were found to be associated with AIS. Stroke localization data collected from patient medical records and magnetic resonance imaging results indicated cortical stroke in 69 children (39 with perinatal ; 30 with childhood AIS) and subcortical stroke in 43 children, being more frequent in childhood (N = 31), compared to perinatal AIS (N = 12). Cortical and subcortical strokes differed in β- fibrinogen −455G>A genotype distributions (p = 0.026), −455AA genotype was identified in cortical stroke only. Difference in PAI-1 4G/5G genotype distributions was found between childhood and perinatal subcortical stroke (p = 0.028), yielding to a 4.80-fold increased risk for childhood subcortical stroke (95% CI: 1.16– 19.92). Obtained results corroborate previously reported FV Leiden association with AIS (Coen Herak et al. Clin Appl Thromb/Hemost, in press) with additional ACE I/D association. Exclusive associations of β-fibrinogen −455AA genotype with cortical stroke and PAI-1 4G/5G with childhood subcortical stroke support the assumption that specific polymorphisms may contribute to location dependant lesion formation.