Warfarin doz ayarlanmasında genetik varyasyonların etkisi

Warfarin en yay gın ku llan ılan ora l antik oa gü lan dır. Dar b ir terapötik in de kse sa h iptir, b u ne den le, warfarin a lan h asta larda antikoa -agü lan yan ıt sık kontro l gere ktirir. Ya ş , cinsiyet, komorb idite ler, b irlik te a lınan ilaçların yan ı sıra farma ko k inetik ve farma ko genetikkogen lerde ki varyasyon lar da warfarin dozunu etkileme kte dir. VKORC1 ve CYP2C9 warfarin meta b o lizmasın dan sorum lu iki gen dir.kiGünümüzde warfarin meta b o lizmasın da k i önem leri ve kliniğe yansıma ları yeterince b ilinmeme kte dir. Bu gen lerde ki po lim o rfizm le rmowarfarine yan ıtta duyarlılığa ve a şırı antikoa gülasyona hatta hemora jik komplikasyonlara neden olmaktadır. Genetik po l m orfizmlimara ş tırması öze llikle uluslararası norma lle ştirilmiş oran (INR) düze yi a yarlanama y an h asta larda fa yda lı o lma kta dır. Farklı ırkklarda vektoplum larda b u iki genin sıklığı da farklıdır. Bu durum warfarine yan ıtta çe şitliliğe ne den o lma kta dır. Günümüzde warfa rin dozuarayarlan ırken h a len genetiğin rolü göz ardı e dilme kte dir. Bu polimorfizm ler için genetik ana liz yapman ın h asta ta kib i ve m a liyetemsa ğlayaca ğı katk ılar h a len tartışma lıdır. Bu konuy la ilgili Amerika ve Avrupada yapılma kta o lan çok merkezli çalışmalar devam etmektedir.

Effect of genetic variations on ad justing of warfarin dose

Warfarin is th e most wide ly use d ora l anticoa gu lant. Since it h as a limite d th erapeutics in dex, anticoa gu lant reaction is mostlyy nee de dyto be controlled in patients takin g warfarin. Besides a ge, gender, medicines taken with comorbidities, the variations in pharmaa cokinet-aics an d ph armaco genetic genes a lso affect th e dose of warfarin. VKORC1 an d CYP2C9 are two genes responsible for warfarinmeta b o lism. To da y th e im portance an d clinica l effects of warfarin in meta b o lism are not known sufficiently. T h e polymorph isms inpth ese genes cause sensitivity an d over anticoagulant even h emorrh agic complication in warfarin reaction. Genetic po lym orph ism mresearch is beneficial especially in patients where international normalized ratio (INR) level cannot be adjusted. The fre q u ency of quthese genes is also different in different races and populations. Thiscondition causes variety in warfarin reaction. Toda y the role ofgenetics is still ignore d in a djustin g warfarin dose. T h e contrib u -tions of doin g genetic ana lysis for polymorph isms to patient fo llowups an d expen diture are still contra dictive. Mu lticentric stu diesa b out th is su bject are going on in th e USA an d Europe .these

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