Genski polimorfizmi i ishemijski moždani udar u djece

Gene polymorphisms and ischemic stroke in children

Cerebrovaskularni poremećaji u djece, iako rijetki, rezultiraju značajnom smrtnošću i dugotrajnim morbiditetom. Pojavnost moždanog udara u djece prema podacima populacijskih studija iznosi 1,23-13,0/100.000 djece/godišnje. Iako je poznato više od 100 rizičnih faktora za nastanak moždanog udara, genetički faktori nisu potpuno istraženi. Za FV Leiden, FII 20210G>A, MTHFR677C>T, manjak protiena C i povišeni lipoprotein (a) pokazano je da igraju ulogu u moždanom udaru u djece. Moždani udar u djece vjerojatno nastaje kao posljedica interakcije više različitih gena i čimbenika okoliša koji zajedno s razlikama u cerebrovaskularnom, neurološkom i koagulacijskom sustavu ograničavaju izravnu ekstrapolaciju istraživanja s odraslih na djecu i opravdaju istraživanja polimorfizama ostalih trombofilijskih faktora. Cilj ovog istraživanja je odrediti prevalenciju genetičkih rizičnih čimbenika u skupini djece s ishemijskim moždanim udarom analizom polimorfizama u i) koagulacijskim faktorima FV (FV Leiden i FV H1299R), FII (20210G>A), FXIII (Val34Leu), beta-fibrinogen (-455G>A) i PAI-1 4G/5G; ii) trombocitni glikoproteinski receptori GPIa (807C>T/873G >A i 52T>C), GPIba (1018C>T, VNTR i (-5C/T Kozak), GPIIb/IIIa (1565T>C – PIA1/A2 i 2622T>G) i GPVI (13254T>C); iii) P-selektin (S290N, N562D, V599L, T715P) i iv) intermedijarni rizični faktori za moždani udar u djece, ACE I/D i Apo E2/E3/E4. Dobiveni rezultati unaprijedit će spoznaju o uključenosti ostalih genetičkih rizičnih čimbenika u etiologiji ishemijskog moždanog udara u djece. Razumijevanje genetičke osnove ishemijskog moždanog udara doprinijet će razvoju i primjeni standardiziranih protokola u dijagnostici, istraživanju, terapiji i procjeni ishoda moždanog udara u djece.

Cerebrovascular disorders in children, although rare, result in significant mortality and long-term morbidity. The incidence of childhood stroke as reported by population based studies is 1.23-13.0/100 000 children/year. More than 100 risk factors for stroke are recognized but genetic factors are incompletely characterized. FV Leiden, FII 20210G>A, MTHFR 677C>T, protein C deficiency and elevated Lp(a) have been demonstrated to play a role in childhood stroke. It is likely that stroke in children occurs secondary to interactions between several genes and the environment that, together with age-related differences in cerebrovascular, neurological and coagulation systems limit the direct extrapolation of research from adults to children and justify research of polymorphisms of other thrombophilic factors. The aim of this investigation is to determine the prevalence of genetic risk factors in a cohort of children with ischemic stroke by analysis of polymorphisms in i) coagulation factors FV (FV Leiden and FV H1299R), FII (20210G>A), FXIII (Val34Leu), ß-fibrinogen (-455G>A) and PAI-1 4G/5G; ii) platelet glycoprotein receptors GPIa (807C>T/873G>A and 52T>C), GPIba (1018C>T, VNTR and (-5)C/T Kozak), GPIIb/IIIa (1565T>C – PIA1/A2 and 2622T>G) and GPVI (13254T>C); iii) P-selectin (S290N, N562D, V599L, T715P) and iv) intermediate risk factors for childhood stroke, ACE I/D and Apo E2/E3/E4. The obtained results will enhance knowledge about involvement of other genetic risk factors in the etiology of ischemic stroke in childhood. The understanding of genetic basis of ischemic stroke will contribute to the development and application of standardized protocols for the diagnosis, investigation, therapy and outcome assessment of ischemic stroke in children.

ischemic stroke, genetic polymorphisms, thrombophilia, children, coagulation