ANALIZA FREKVENCIJE ALELA CYP2D6*4 KOD BOLESNIKA SA SHIZOFRENIJOM
Sažetak
Superfamilija enzima citohroma P450 uključena je u metabolizam niza endogenih i egzogenih supstrata. Varijanta CYP2D6 uključena je u metabolizam desetina lekova, kao što su triciklični antidepresivi, antipsihotici, beta blokatori, antiaritmici, antidijabetici, lekovi protiv karcinoma i tako dalje. Enzim CYP2D6 pokazuje visok polimorfizam i najčešća varijanta alela CYP2D6*4 je spor metabolizator (SM). SM uzrokuje smanjenje terapijskog odgovora, povećava rizik od neželjenih reakcija na lek i povećava koncentraciju leka i njegovih metabolita u plazmi, iznad nivoa toksičnosti. Cilj ove studije bila je analiza učestalosti alela CIP2D6*4 kod bolesnika sa shizofrenijom, radi dalje individualizacije i racionalizacije terapije. U ispitivanje je uključeno 38 bolesnika sa shizofrenijom i 110 zdravih osoba. PCR specifičan za alel korišćen je za detekciju alela CYP2D6*4. Kod 55% bolesnika sa shizofrenijom pronašli smo oba nosioca alela divljeg tipa, kod 45% heterozigot divlji tip/*4, dok homozigot *4/*4 nije identifikovan. Uočena je statistički značajna razlika u distribuciji genotipa (p < 0,05) između shizofrenih bolesnika i zdravih osoba. Učestalost alela *4 (37%) značajno je veća kod obolelih od shzofrenije u poređenju sa ispitanicima kontrolne grupe, što ukazuje na oprez u primeni supstrata CYP2D6. Niža učestalost SM kod shizofrenih bolesnika, nego kod zdravih osoba može se objasniti metabolizmom neuroaktivnog supstrata CYP2D6. Međutim, 45% bolesnika sa shizofrenijom, koji su srednji metabolizatori, nosi veći rizik od neželjenog odgovora na supstrate CYP2D6, u poređenju sa divljim tipom. Kako nijedan od analiziranih bolesnika nije bio SM, može se zaključiti da su bolesnici primali adekvatne doze leka.
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