The prevalence and significance of genetic polymorphisms of vascular homeostasis and lipid metabolism in acute ischemic stroke

Ishemijski moždani udar je multifaktorijalna bolest koja se razvija međudjelovanjem genske osnove i okolišnih čimbenika rizika. U nastanak i razvoj moždanog udara uključeni su sustavi zgrušavanja i fibrinolize, upalnog odgovora, metabolizma lipida, regulacije krvnog pritiska. Do sada je znanstvenoj literaturi opisano više desetaka potencijalnih genskih čimbenika rizika za nastanak moždanog udara, ali je njihova pojedinačna povezanost s moždanim udarom slaba. Ciljevi ovog istraživanja bili su ispitati: učestalost varijanti F5 Leiden, G20210A gena F2, V34L gena F13A1, -445G/A gena FGB, 5G/4G gena SERPINE1, I/D gena ACE i -1131T/C gena APOA5 u zdravih ispitanika i ispitanika s ishemijskim moždanim udarom; razliku u koncentraciji lipidnih parametara (ukupni kolesterol, HDL- i LDL-kolestrol i trigliceridi) i parametara upale (CRP i broj leukocita); povezanost genskih čimbenika, lipidnih parametara i parametara upale s nastankom moždanog udara. U istraživanje je uključeno 250 ispitanika kojima je dijagnosticiran ishemijski moždani udar na osnovu kliničkog pregleda i kompjuterizirane tomografije i 100 zdravih ispitanika regrutiranih tijekom sistematskog pregleda bez podatka o cerebrovaskularnom i/ili kardiovaskularnom incidentu u osobnoj anamnezi. Svim ispitanicima su natašte uzeti uzorci krvi za genotipizaciju i određivanje lipidnog statusa, CRP-a i broja leukocita. Rezultati su pokazali da ispitanici s moždanim udarom imaju značajno niže koncentracije ukupnog kolesterola i LDL-kolesterola i značajno više koncentracije glukoze i CRP-a te značajno veći broj leukocita u odnosu na kontrolne ispitanike. Varijanta I/D gena ACE povezana je s težinom moždanog udara, a varijanta -1131 T/C gena APOA5 je uz dob i pretilost neovisan čimbenik nastanka teškog ishemijskog moždanog udara. Nije pronađena razlika u učestalosti ispitivanih genskih čimbenika između ispitanika s moždanim udarom i kontrolnih ispitanika.Stroke is a multifactorial disease developing through the complex interaction of both genetic and environmental risk factors. Initiation and progression of stroke involves disorders in coagulation cascade, fibrinolytic system, inflammatory response, lipid metabolism and blood pressure homeostasis. Until today a large number of potential genetic risk markers have been studied but their individual association with stroke is weak. We aimed to investigate: the prevalence of F5 Leiden, F2 G20210A, F13A1 V34L, FGB -455G/A, SERPINE1 5G/4G, ACE I/D and APOA5 -1131T/C variants in healthy subjects and subjects with acute ishemic stroke; differences in blood lipid concentrations (total, HDL- and LDL-cholesterol and triglycerides) and inflammatory markers (CRP and white blood cell count); association of genetic variations, blood lipids and inflammatory markers with the ischemic stroke risk. The study included 250 subjects with acute ishemic stroke which was diagnosed by clinical examination and computerized tomography and 100 healthy subjects without known cerebrovascular and/or cardiovascular incidents in anamnesis regruted during general medical examination. Blood samples for genotyping and determination of blood lipids, CRP and WBC count were drawn to all subjects in fasting state. Results have shown that subjects with acute ishemic stroke have significantly lower concentrations of total and LDL-cholestrol whereas concentrations of glucose, CRP and WBC are significantly higher than in control subjects. ACE variant I/D has shown association with the stroke severity. APOA5 variant -1131T/C along with age and obesity is independent predictor of severe stroke. There are no differences in the frequencies of the investigated genetic variants between studied groups of subjects