engleski

Polymorphisms in Coagulation Factor Genes and Enzymes of Homocysteine Metabolism in Croatian Children with Arterial Ischemic Stroke

Despite extensive investigations and identification of a wide range of inherited and acquired risk factors for childhood stroke in recent years, genetic risk factors for this disease are still incompletely characterized. Taking into consideration that the frequency of genetic factors may vary among different populations, the aim of this study was to investigate the possible role of individual inherited prothrombotic and intermediate risk factors in Croatian children with a confirmed diagnosis of arterial ischemic stroke (AIS) and to check the possible association of investigated risk factors with the disease. A genotype analysis of 14 polymorphisms in 12 candidate genes encoding proteins of the coagulation and fibrinolysis systems (FV Leiden, FV HR2, FII G20210A, b-FBG −455G>A, FXIII-A Val34Leu, PAI-1 4G/5G), human platelet alloantigens (HPA-1, -2, -3 and -5), homocysteine metabolism (MTHFR C677T, MTHFR A1298C) and intermediate risk factors (ACE I/D and apoE e2–4) was performed in 73 children (48 boys and 25 girls) with AIS aged ≤18 years and compared with 100 age- and sex-matched control subjects from the same geographical region. Investigated polymorphisms were also analyzed in AIS subgroups defined according to the time of stroke onset into perinatal (n = 35, 20 boys and 15 girls) and childhood AIS (n = 38, 28 boys and 10 girls). FV Leiden was found to be significantly associated with approximately 5-fold increased risk for AIS (OR = 4.72 ; 95% CI 1.22–18.27), and 8-fold increased risk for perinatal AIS (OR = 8.29 ; 95% CI 1.95–35.24). The presence of at least one HPA-3b allele was associated with approximately 2-fold lower risk for the development of AIS (OR = 0.51 ; 95% CI 0.26–0.98) and perinatal AIS (OR = 0.40 ; 95% CI 0.18–0.92). Increased risk for childhood AIS was identified in carriers of at least one FXIII-A Leu34 allele (OR = 2.21 ; 95% CI 1.03–4.73). Moreover, combined heterozygosity for FV Leiden and FV HR2 was found in 5/73 children with AIS (P = 0.012), in both AIS subgroups (perinatal AIS 2/35, childhood AIS 3/35) whereas this combination was not found in control subjects. This case-control study confirmed the association between FV Leiden and AIS that has also been observed in numerous studies so far, but it also showed that other previously not reported polymorhisms (FXIII-A Val34Leu, HPA-3) as well as the combination of FV Leiden and FV HR2 polymorphisms, can be related to AIS subgroups in Croatian population.

stroke; child; risk factors; coagulation factors; homocysteine

Oral communications - oral poster presentation ; http://dx.doi.org/10.1016/S0049-3848(14)50088-6 ; doi:10.1016/S0049-3848(14)50088-6