Distribucija polimorfizma gena koji kodiraju CYP3A5, CYP3A4 i P-glikoprotein kod bolesnika podvrgnutih transplantaciji bubrega
Sažetak
Uvod/Cilj. Polimorfizmi gena koji kodiraju transporter P-glikoprotein i najvažnije enzime za farmakokinetiku takrolimusa mogu imati značajan uticaj koji se odražava na koncentracije ovog leka u krvi. Cilj ovog ispitivanja bio je da se ispita učestalost polimorfizma gena CYP3A5, CYP3A4 i ABCB1 kod bolesnika sa transplantiranim bubregom, po prvi put u našem centru za transplantaciju. Metode. Urađena je prospektivna studija preseka koja je obuhvatila 211 bolesnika sa urađenom transplantacijom bubrega u Centru za transplantaciju solidnih organa Vojnomedicinske akademije u Beogradu. U studiju su bili uključeni bolesnici oba pola, starosti od 22 do 69 godina, bele rase i na imunosupresivnom režimu koji uključuje takrolimus. Urađena je genotipizacija CYP3A5 6986A>G (*3 ili *1, rs776746), CYP3A4 -392A>G (*1 ili *1B, rs2740574) i ABCB1 3435C>T (rs1045642) korišćenjem TaqMan® eseja za određivanje pojedinačnih nukleotidnih polimorfizama. Rezultati. Većina naših bolesnika (94,8%) imala je funkcionalan CYP3А4 enzim, dok je kod 87,7% od svih naših bolesnika CYP3A5 bio sa oštećenom aktivnošću. S druge strane, kod oko trećine (31,3%) bolesnika ABCB1 transporter bio je funkcionalan. Zaključak. Ukupno 84,8% naših bolesnika imalo je istovremeno CYP3A5*3*3 genotip, povezan sa smanjenom CYP3A5 aktivnošću, i CYP3A4*1*1/*1*1B genotip, povezan sa funkcionalnom formom CYP3A4 enzima, dok je od svih bolesnika sa smanjenom CYPA5 enzimskom aktivnošću 68,7% imalo smanjenu aktivnost ABCB1 transportera. Međutim, buduće studije su neophodne kako bi se pokazao uticaj ovih genskih polimorfizama na koncentraciju takrolimusa u krvi bolesnika nakon transplantacije bubrega.
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