Frequency of vitamin K oxidoreductase complex subunit-1 (VKORC1) polymorphisms and warfarin dose management in patients with venous thromboembolism

被引：3

作者：

Kabalak, Pinar Akin ^{[1
]}

Savas, Ismail ^{[2
]}

Akar, Nejat ^{[3
]}

Demir, Nalan ^{[4
]}

Egin, Yonca ^{[5
]}

机构：

[1] Med Sci Univ, Ataturk Chest Dis & Surg Training & Res Hosp, Ankara, Turkey

[2] Ankara Univ, Dept Chest Dis, Sch Med, Ankara, Turkey

[3] TOBB Econ & Technol Univ Hosp, Dept Pediat, Ankara, Turkey

[4] Osmangazi Univ, Sch Med, Dept Intens Care, Eskisehir, Turkey

[5] Ankara Univ, Sch Med, Dept Pediat Mol Genet, Ankara, Turkey

来源：

PHARMACOGENOMICS JOURNAL | 2018年 / 18卷 / 05期

关键词：

CYP2C9; REQUIREMENTS; IMPACT; MAINTENANCE; CYP4F2;

D O I：

10.1038/s41397-018-0037-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Warfarin works by inhibiting VKORC1, so polymorphisms of this gene modify the required drug dose. The aim of this study is to examine the relation between therapeutic weekly dose of warfarin and C1173T/G1639A polymorphism of VKORC1 in patients with VTE. Seventy-five patients with VTE were enrolled. Weekly warfarin doses and time (day) to reach therapeutic INR were evaluated retrospectively along with VKORC1-C1173T and G1639A alleles. The mean weekly warfarin dose was lower and time to reach therapeutic INR was shorter in homozygote alleles (AA and TT) (p < 0 .05) . The multivariate regression model was produced, R-2 = 0.05% for age (p = 0.04), R-2 = 6% for VKORC1 (p = 0.03), the model for estimating warfarin dose R-2 = 17% (p > 0.05). In particular, patients who need overdose of warfarin or whose bleeding score is high, study of these polymorphisms can be considered.

引用

页码：646 / 651

页数：6

共 17 条

[1] NATURAL-HISTORY OF PULMONARY-EMBOLISM [J].

DALEN, JE ;

ALPERT, JS .

PROGRESS IN CARDIOVASCULAR DISEASES, 1975, 17 (04) :259-270

[2] AGING AND THE ANTICOAGULANT RESPONSE TO WARFARIN THERAPY [J].

GURWITZ, JH ;

AVORN, J ;

ROSSDEGNAN, D ;

CHOODNOVSKIY, I ;

ANSELL, J .

ANNALS OF INTERNAL MEDICINE, 1992, 116 (11) :901-904

[3] Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert Panel Report [J].

Kearon, Clive ;

Akl, Elie A. ;

Ornelas, Joseph ;

Blaivas, Allen ;

Jimenez, David ;

Bounameaux, Henri ;

Huisman, Menno ;

King, Christopher S. ;

Morris, Timothy A. ;

Sood, Namita ;

Stevens, Scott M. ;

Vintch, Janine R. E. ;

Wells, Philip ;

Woller, Scott C. ;

Moores, Lisa .

CHEST, 2016, 149 (02) :315-352

[4]

Lefebvre S., 2016, COMP BIOL RESISTANCE, P19, DOI [10.5772/64204, DOI 10.5772/64204]

[5] Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans [J].

Limdi, Nita A. ;

KArnett, Donna ;

Goldstein, Joyce A. ;

Beasley, T. Mark ;

McGwin, Gerald ;

Adler, Brian K. ;

Acton, Ronald T. .

PHARMACOGENOMICS, 2008, 9 (05) :511-526

[6] Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients [J].

Natarajan, Sripriya ;

Ponde, Chandrashekhar K. ;

Rajani, Rajesh M. ;

Jijina, Farah ;

Gursahani, Roopkumar ;

Dhairyawan, Pradnya P. ;

Ashavaid, Tester F. .

PHARMACOLOGICAL REPORTS, 2013, 65 (05) :1375-1382

[7] Impact of Genetic Factors (CYP2C9, VKORC1 and CYP4F2) on Warfarin Dose Requirement in the Turkish Population [J].

Ozer, Mahmut ;

Demirci, Yeliz ;

Hizel, Candan ;

Sarikaya, Sabit ;

Karalti, Iskender ;

Kaspar, Cigdem ;

Alpan, Serdar ;

Genc, Ece .

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2013, 112 (03) :209-214

[8] The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements in an adult Turkish population [J].

Ozer, Nihat ;

Cam, Nese ;

Tangurek, Burak ;

Ozer, Songul ;

Uyarel, Huseyin ;

Oz, Dilaver ;

Guney, Mehmet Rasit ;

Ciloglu, Figen .

HEART AND VESSELS, 2010, 25 (02) :155-162

[9] VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients [J].

Ozgon, G. Oner ;

Langaee, T. Y. ;

Feng, H. ;

Buyru, N. ;

Ulutin, T. ;

Hatemi, A. C. ;

Siva, A. ;

Saip, S. ;

Johnson, J. A. .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2008, 64 (09) :889-894

[10] The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients [J].

Prandoni, Paolo ;

Noventa, Franco ;

Ghirarduzzi, Angelo ;

Pengo, Vittorio ;

Bernardi, Enrico ;

Pesavento, Raffaele ;

Iotti, Matteo ;

Tormene, Daniela ;

Simioni, Paolo ;

Pagnan, Antonio .

HAEMATOLOGICA, 2007, 92 (02) :199-205

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