Naslov
Association of Polymorphisms in Coagulation Factor Genes and Enzymes of Homocysteine Metabolism With Arterial Ischemic Stroke in Children

Autori
Coen Herak, Desiree ; Leniček Krleža, Jasna ; Radić Antolić, Margareta ; Horvat, Ivana ; Đuranović, Vlasta ; Zrinski Topić, Renata ; Zadro, Renata

Izvornik
Clinical and applied thrombosis/hemostasis (1076-0296) 23 (2017), 8; 1042-1051

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
arterial ischemic stroke ; children ; genetic polymorphisms ; coagulation factors ; homocysteine metabolism

Sažetak
Despite the identification of a wide range of inherited and acquired risk factors for arterial ischemic stroke (AIS) in children, genetic risk factors are incompletely characterized and may vary among different populations. We investigated the role of individual and combined inherited prothrombotic and intermediate-risk factors in 73 children with perinatal (n ¼ 35) and childhood AIS (n ¼ 38) and 100 age- and sex- matched controls. Ten polymorphisms in 8 candidate genes encoding coagulation and fibrinolytic proteins (factor V [FV] Leiden, FV HR2, factor II [FII] G20210A, b- fibrinogen [b-FBG]-455G>A, factor XIII [FXIII]- A p.Val34Leu, plasminogen activator inhibitor 1 4G/5G), homocysteine metabolism (methylenetetrahydrofolate reductase [MTHFR] C677T, MTHFR A1298C), and intermediate- risk factors (angiotensin-converting enzyme I/D, apoE e2-4) were detected using a multilocus genotyping assay. Allele- specific polymerase chain reaction was used for the determination of human platelet alloantigens (HPA-1, HPA-2, HPA-3, and HPA-5). Factor V Leiden was associated with an increased risk of AIS (odds ratio [OR]: 4.72, 95% confidence interval [CI]: 1.22-18.27) and perinatal AIS (OR: 8.29, 95% CI: 1.95- 35.24). Human platelet antigen-3b allele carriers had a 2-fold lower risk of AIS (OR: 0.51, 95% CI: 0.26-0.98) and perinatal AIS (OR: 0.40, 95% CI: 0.18-0.92). A 2.21-fold increased risk of childhood AIS (95% CI: 1.03- 4.73) was identified in FXIII-A Leu34 allele carriers. Combined FV Leiden/FV HR2, FV Leiden/MTHFR A1298C, FV Leiden/MTHFR C677T/MTHFR A1298C, and FV Leiden/FV HR2/MTHFR A1298C heterozygosity was identified in children with AIS but not in controls, which revealed a statistically significant difference. This case– control study shows that besides already documented association between FV Leiden and AIS, other previously unreported polymorphisms (FXIII-A p.Val34Leu, HPA-3) and several genotype combinations that always include heterozygous FV Leiden can be related to AIS in Croatian population.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA