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Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients

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

Abstract

Objective

African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa.

Material and methods

The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients.

Results

Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P < 0.001). SNPs around the VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P <0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P < 0.001), body weight (P = 0.04), target INR (P = 0.007), and concurrent medications (P = 0.029) could explain about 36.7% of the total warfarin dose variation.

Conclusion

Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.

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Acknowledgments

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A030001). We are grateful to all doctors, nurses, and patients from Ahmed Gasim Hospital and Sudan Heart Centre who participated in this study.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-dong, Gangnam-gu, Seoul, 135–710, South Korea

    Nassr Eldin M. A. Shrif, Seung-Tae Lee, Ka-Kyung Kim, Soo-Youn Lee, Chang-Seok Ki & Jong-Won Kim

  2. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea

    Hong-Hee Won, Jun-Hee Park, Ka-Kyung Kim, Min-Ji Kim & Seonwoo Kim

  3. Radio-Isotope Centre Khartoum (RICK), Khartoum, Sudan

    Ihsan M. Osman & Enaam A. Rhman

  4. Department of Medicine, International University of Africa, Faculty of Medicine and Health Sciences, Khartoum, Sudan

    Ibtisam A. Ali

  5. Department of Neurology, Medicine, University of Khartoum, Khartoum, Sudan

    M. N. A. Idris

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  1. Nassr Eldin M. A. Shrif
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Correspondence to Jong-Won Kim.

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Shrif, N.E.M.A., Won, HH., Lee, ST. et al. Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients. Eur J Clin Pharmacol 67, 1119–1130 (2011). https://doi.org/10.1007/s00228-011-1060-1

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