Polimorfizmi u genu za apolipoprotein E kao faktori rizika od ateroskleroze karotidnih arterija
Sažetak
Uvod/Cilj. Ateroskleroza je vodeći uzročnik smrtnosti u zapadnom svetu. Proces formiranja aterosklerotskog plaka podrazumeva akumulaciju ćelija inflamatornog odgovora, lipida, glatkih mišićnih ćelija i proteina vanćelijskog matriksa u intimi zida krvnog suda. Apolipoprotein E učestvuje u transportu egzogenog holesterola, endogeno sintetisanih lipida i triglicerida u organizmu. Gen koji kodira apolipoprotein E smatra se jednim od gena kandidata u izučavanju ateroskleroze. Rezultati prethodnih studija, urađenih na različitim populacijama, jasno ukazuju da su varijacije u genu za apolipoprotein E glavni modulatori nivoa lipoproteina male gustine u serumu. Do sada objavljeni rezultati koji se tiču povezanosti polimorfizama u genu za apolipoprotein E sa aterosklerozom karotidnih arterija su kontradiktorni. Zato je cilj ove studije bio da se ispita povezanost polimorfizama u genu za apolipoprotein E sa rizikom od nastanka aterosklerotskog plaka u karotidnim arterijama kao i sa nivoom proteina apolipoprotein E i lipida u serumu bolesnika sa aterosklerozom karotidnih arterija iz Srbije. Metode. Ovom studijom bilo je obuhvaćeno ukupno 495 ispitanika: 285 zdravih ispitanika u kontrolnoj grupi i 210 bolesnika sa aterosklerozom karotidnih arterija koji su bili upućeni na endarterektomiju. Genotipizacija polimorfizama u genu za apolipoprotein E je urađena metodama lančane reakcije polimeraze i analizom fragmenata dobijenih digestijom sa restrikcionim enzimima. Rezultati. Bolesnici su imali statistički značajno manju frekvenciju alela ε2 u odnosu na kontrolnu grupu. Ispitanici koji su bili nosioci genotipa sa bar jednom kopijom alela ε2 imali su statistički značajno viši nivo proteina apolipoprotein E i statistički značajno niži nivo lipoproteina male gustine u serumu u odnosu na bolesnike koji su bili nosioci genotipova bez prisustva alela ε2. Zaključak. Rezultati ove studije ukazuju na zaštitni efekat alela ε2 od nastanka aterosklerotskog plaka u karotidnim arterijama, kao i povezanost sa nižim nivoom lipoproteina male gustine u serumu bolesnika sa njihovom aterosklerozom. Neophodna su dalja istraživanja gena i faktora rizika iz spoljašnje sredine uključenih u nastanak ateroskleroze u različitim populacijama.
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