Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage

• Published in: European journal of clinical pharmacology 2013-05, Vol.69 (5), p.1113-1120
• Main Authors: Wang, Lian Sheng, Shang, Jing Jing, Shi, Shu Ya, Zhang, Yan Qing, Lin, Jian, Guo, Zhi Hua, Wang, Yi Chen, Tang, Jie, Liu, Jie, Liu, Ying Zi, Li, Zhi, Tan, Zhi Rong, Zhou, Hong Hao, Jiang, Hai He, Xie, Hai Tang
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anticoagulants - administration & dosage; Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group - genetics; Binding sites; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug therapy; Female; Genes; Humans; Maintenance Chemotherapy; Male; Medical sciences; Middle Aged; Mixed Function Oxygenases - genetics; Orosomucoid - genetics; Pharmacogenetics; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymorphism, Genetic - genetics; Proteins; Vitamin K Epoxide Reductases; Warfarin - administration & dosage
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-012-1448-6

Purpose ORM1 is a plasma drug binding protein. Its polymorphism rs17650 (* S >* F ) has been reported to be an important factor affecting the binding ability and effect of antiretroviral protease inhibitors. The aim of this study was to determine whether the ORM1 rs17650 polymorphism also influences warfarin therapy. Methods A total of 191 Chinese patients with steady-dose warfarin therapy were enrolled in this study. The patients were studied for warfarin maintenance dose, the ORM1 rs17650 polymorphism, and two polymorphisms previously demonstrated to affect warfarin response [ CYP2C9 rs1057910 (* 3 ) and VKORC1 rs7294 (− 1639 G > A )]. Results Warfarin dose was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910 and ORM1 rs17650 polymorphisms. Patients carrying the wild-type of these three genes ( n = 96) took a mean dose of 3.0 ± 1.1 mg warfarin, which was significantly higher than that taken by the 52 * S patients (2.7 ± 0.7) and 11 * S * S patients (2.5 ± 0.6 mg) (p = 0.048). Conclusion We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 * S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.