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Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals

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Abstract

Background and Objective

Warfarin is the most widely prescribed oral anticoagulant worldwide. The narrow therapeutic index and the large variation in the inter-individual dose of warfarin are problematic, since the side effects can be lethal. Single nucleotide polymorphisms (SNP) in CYP2C9 and VKORC1 have been shown to significantly affect warfarin dosage toleration and this effect varies among different populations. We aimed to investigate the effect of these SNPs on warfarin dosage in a sample of Kuwaiti patients.

Methods

Kuwaiti patients who were taking a maintenance dose of warfarin were genotyped for CYP2C9*1, *2 and *3 and VKORC1 rs9923231, rs9934438, rs7294 and rs2884737. The association of these SNPs with the warfarin dose was evaluated.

Results

For CYP2C9, the CYP2C9 *1/*1 genotype required a higher dose (5.5 ± 3.3 mg/day) compared to non-*1/*1 (3.3 ± 1.7 mg/day) (p = 0.003). For VKORC1, the daily warfarin dose was significantly different (p = 0.001) among the three genotypes of rs9923231, rs9934438 and rs2884737, with carriers of the wild-type genotype requiring the highest dose compared to variant allele carriers (p ≤ 0.001–0.002). There was no association found between the daily warfarin dose and the rs7294 polymorphism.

Conclusions

Our data showed that individuals carrying the wild-type allele of CYP2C9 or VKORC1 rs9923231, rs9934438 or rs2884737 are less sensitive than individuals with the variant alleles of these SNPs and therefore required a higher daily maintenance dose of warfarin. Our study confirms the association between SNPs in CYP2C9 and VKORC1 and warfarin dose tolerance in Kuwaiti patients.

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Acknowledgments

We would like to extend our deepest appreciation and gratitude to the staff at Mubarak Al-Kabeer and Al-Ameri Hospitals in Kuwait for their assistance with the blood collection and patient data collection. We would also like to thank Mrs. Jeethu Anu George for her technical assistance.

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Authors and Affiliations

  1. Department of Biological Sciences, Faculty of Science, Kuwait University, PO Box 5969, Safat, 13060, Kuwait, Kuwait

    Maryam H. Alrashid, Philip Koshi & Suzanne A. Al-Bustan

  2. Department of Pathology, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Ahmad Al-Serri

  3. Department of Medicine, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Salem H. Alshemmari

Authors
  1. Maryam H. Alrashid
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  2. Ahmad Al-Serri
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  3. Salem H. Alshemmari
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  4. Philip Koshi
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Corresponding author

Correspondence to Maryam H. Alrashid.

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Conflict of interest

The authors declare that they have no conflict of interest to report.

Funding

This research was fully funded by Kuwait University Research Administration, Project MM 01/08. The use of the ABI 3130xl Gene Analyzer was under and the General Facility Project grant GS 01/02.

Ethical approval and informed consent

Approval for this study was obtained from the Joint Committee for The Protection of Human Subjects in Research of the Health Sciences Centre (HSC) and the Kuwait Institute of Medical Specialization (KIMS) following the guidelines set by the Declaration of Helsinki. All patients who participated in the study provided informed consent.

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Alrashid, M.H., Al-Serri, A., Alshemmari, S.H. et al. Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals. Mol Diagn Ther 20, 183–190 (2016). https://doi.org/10.1007/s40291-016-0190-7

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  • DOI: https://doi.org/10.1007/s40291-016-0190-7

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