Genetski biljezi ateroskleroze u cerebrovaskularnoj bolesti

Bazina, Antonela (2015) Genetski biljezi ateroskleroze u cerebrovaskularnoj bolesti. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The etiology of ischemic stroke (IS) is multifactorial. Different genes and their polymorphisms, individual characteristics, inflammatory processes, and their interactions play an important, but still insufficiently apparent role in the development of stroke. PPAR-γ regulates the expression of key genes involved in inflammation and immunity, metabolism of sugar and fat, and adipogenesis. IL-6, ACE, MTHFR and APOE belong to different PPARγ target gene. The aim of our study was to estimate the influence of interactions between the PPAR-γ gene variants, its target genes IL-6, ACE, APOE and MTHFR and conventional risk factors in the development of ischemic stroke. The study included 301 participants (114 with IS and 187 controls). Genotyping of PPAR-γ Pro12Ala, IL-6 -174G>C, ACE I/D, APOE E2, E3, E4 and MTHFR C677T was performed by using polymerase chain reaction base methods. Statistically significant predictors of IS were male gender, hypertension, lowered HDL cholesterol, elevated C-reactive proteina, PPARγ Pro12Ala, IL-6 -174 G>C genotype. The male gender to female increases the likelihood of stroke by 10%, the presence of hypertension increased by 37.3 times, Pro12Ala PPARγ genotype had a protective effect and reduced the likelihood of stroke by 90% while the GC genotype of IL-6 increased the likelihood of the same for 9.3 times. There was no statistically significant correlation between MTHFR gene, ACE, APOE and their polymorphisms in the incidence of stroke.

Abstract in Croatian

Etiologija ishemijskog moždanoga udara (IMU) je multifaktorijalna. Različiti geni, njihovi polimorfizmi, karakteristike pojedinca, upalni procesi te njihove međusobne interakcije igraju važnu, no i dalje do kraja nerazjašnjenju ulogu u razvoju moždanog udara. PPAR-γ regulira ekspresiju ključnih gena u upali i imunosti, metabolizmu šećera i masti, te u adipogenezi. Među različite ciljane gene PPAR-γ pripadaju i IL-6, ACE, APOE, MTHFR. Cilj naše studije bio je ispitati interakcije između varijanti gena transkripcijskog faktora PPAR-γ i njegovih ciljnih gena IL-6, ACE, APOE i MTHFR, te interakcije pojedinih gena i praćenih konvencionalnih rizničnih čimbenika u razvoju ishemijskog moždanog udara. Istraživanje je provedeno na 301 ispitaniku (114 s IMU i 187 kontrola). Genotipizacija PPARγ Pro12Ala, IL-6 -174G>C, ACE I/D, APOE E2, E3, E4 i MTHFR C677T provedena je metodama temeljenima na lančanoj reakciji polimerazom. Statistički značajni prediktori moždanog udara bili su muški spol, hipertenzija, sniženi HDL, povišena razina CRP-a, IL-6 -174 G>C, PPARγ Pro12Ala genotip. Muški spol u odonosu na ženski povećava vjerojatnost MU za 10%, prisutnost hipertenzije povećava za 37.3 puta, genotip Pro12Ala PPAR-γ imao je protektivni učinak i umanjivao vjerojatnost pojave MU za 90%, dok je genotip GC IL-6 povećavao vjerojatnost pojave istog za 9.3 puta. Nije nađena statistički značajna povezanost gena MTHFR, ACE, APOE i njihovih polimorfizama s pojavnošću moždanog udara.

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