Journal of Iranian Blood Transfusion

fa ارزیابی پلی‌مورفیسم‌های رایج ژن CYP2C9 در بیماران تحت درمان با داروی وارفارین Evaluation of common polymorphism of CYP2C9 in Warfarin-treated patients هماتولوژي Hematology پژوهشي Research چکیده سابقه و هدف امروزه وارفارین به طور وسیعی توسط پزشکان تجویز میشود. عوامل مختلفی هم‌چون سن، جنس، رژیمغذایی، داروهای مصرفی و از همه مهمتر عوامل ژنتیکی در تعیین دوز وارفارین مؤثر میباشند. از عوامل مؤثر ژنتیکی میتوان به سه آلل اصلی ژن CYP2C9 اشاره نمود. با توجه به روند رو به پیشرفت بیماری قلبی، این مطالعه جهت ارزیابی پلی‌مورفیسم‌های رایج در بیماران تحت درمان با وارفارین انجام شد. مواد و روش‌ها مطالعه تجربی حاضر در سال 1390-1389در آزمایشگاه پیوند انجام گرفت. بیماران به دلایل مختلف از جمله مشکلات قلبی وارفارین دریافت میکردند. پلیمورفیسمهای ژن CYP2C9 به روش PCR-RFLP مورد بررسی قرار گرفتند و در نهایت یافته‌ها توسط نرمافزار 13 SPSS و آزمون آماری t-test تجزیه و تحلیل شدند. یافته‌ها مطالعه بر روی 100 بیمار انجام شده بود که 3/47% آن‌ها مؤنث و 7/52% آن‌ها مذکر بودند. فراوانی افراد با آلل *1*1 ، *1*2 ، *1*3 و *2*3 برای ژن CYP2C9 به ترتیب 42/68% ، 52/10%، 94/18% و 1/2% بود. دوز روزانه وارفارین مصرفی در افراد با آلل *1*1 بیشتر از افراد با آلل *1*2 ، *1*3 و *2*3 بود(02/0 p= ؛ 57/1 ± 58/4 میلی‌گرم در روز). نتیجه گیری نتایج تحقیق نشان داد حضور پلیمورفیسم ژن CYP2C9 اثر مهمی بر دوز وارفارین مورد نیاز برای حفظ INR در محدوده 3-2 دارد. در این مطالعه آلل *1*2 CYP2C9 شایعترین پلیمورفیسمهای موجود بود ولی افراد با ژنوتیپهای *2*2 و *2*3 نیز وجود دارند که اهمیت نیاز به بررسی ژنوتیپ وارفارین را در جامعه ایرانی نشان میدهد. Abstract Background and Objectives Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons. Materials and Methods The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory. Results Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day p= 0.02) as compared to other CYP2C9 genotypes. Conclusions The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients. Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K Abstract Background and Objectives Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons. Materials and Methods The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory. Results Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day p= 0.02) as compared to other CYP2C9 genotypes. Conclusions The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients. Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K Abstract Background and Objectives Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons. Materials and Methods The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory. Results Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day p= 0.02) as compared to other CYP2C9 genotypes. Conclusions The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients. کلمات کلیدی: وارفارین, ژنتیک پلیمورفیسم, پروتئینCYP2C9 انسانی , ویتامین K Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K 340 346 http://bloodjournal.ir/browse.php?a_code=A-10-864-1&slc_lang=fa&sid=1 F. Rad فریبا راد 9100319475328460013353 9100319475328460013353 No یاسوج ـ ایران M. Hamidpour محسن حمیدپور 9100319475328460013354 9100319475328460013354 No تهران ـ ایران H. Saadat حبیب‌اله سعادت 9100319475328460013355 9100319475328460013355 No تهران ـ ایران B. Poopak بهزاد پوپک bpoopak@yahoo.com 9100319475328460013356 9100319475328460013356 Yes تهران ـ ایران ـ صندوق پستی: 1495/19395