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Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Funding

This study was supported by National Natural Science Foundation of China grant 81072707, 81173134 and 81070902.

Competing interests

None.

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Authors and Affiliations

  1. Pharmacogenetics Research Institute, Institute of Clinical Pharmacology of Central South University, Changsha, China

    Lian Sheng Wang, Jing Jing Shang, Shu Ya Shi, Yan Qing Zhang, Jian Lin, Zhi Hua Guo, Yi Chen Wang, Jie Tang, Jie Liu, Ying Zi Liu, Zhi Li, Zhi Rong Tan & Hong Hao Zhou

  2. Department of Cardiothoracic Surgery, First XiangYa Hospital, Central South University, Changsha, China

    Hai He Jiang

  3. Department of Clinical Pharmacy and Pharmacology, Anhui Provincial Center for Drug Clinical Evaluation, Yi Ji Shan Hospital, Wan Nan Medical College, Wuhu, China

    Hai Tang Xie

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  1. Lian Sheng Wang
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Correspondence to Lian Sheng Wang.

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Wang, L.S., Shang, J.J., Shi, S.Y. et al. Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage. Eur J Clin Pharmacol 69, 1113–1120 (2013). https://doi.org/10.1007/s00228-012-1448-6

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  • DOI: https://doi.org/10.1007/s00228-012-1448-6

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