Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose

Proposal for a new dosing regimen

M. S. El Din, Dalia G. Amin, S. B. Ragab, E. E. Ashour, M. H. Mohamed, A. M. Mohamed

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

Introduction: Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9(*2 and CYP2C9(*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage. Methods: A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9(*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9(*2 allele. Results: VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% ((*1\(*1), 3.3% ((*1\(*2), 9.7% (*1\(*3), 4.5% ((*2\(*2) and 0.65% (2\(*3 and (*3\(*3). VKORC1 TT and CYP2C9(*2\(*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability. Conclusion: VKORC1-TT and CYP2C9 (*1/(*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.

Original languageEnglish
Pages (from-to)517-524
Number of pages8
JournalInternational Journal of Laboratory Hematology
Volume34
Issue number5
DOIs
Publication statusPublished - 1 Oct 2012

Fingerprint

Genetic Polymorphisms
Warfarin
Polymorphism
Genotype
Polymerase chain reaction
Assays
Cytochrome P-450 CYP2C9
Gene Frequency
Anticoagulants
Haplotypes
Real-Time Polymerase Chain Reaction
Stroke
Alleles
Hemorrhage
Polymerase Chain Reaction
Pharmaceutical Preparations
Population

Keywords

  • CYP2C9
  • Real-time PCR
  • VKORC1
  • Warfarin

Cite this

@article{85d1e601dffd4b88b9aa458eaed637ea,
title = "Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: Proposal for a new dosing regimen",
abstract = "Introduction: Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9(*2 and CYP2C9(*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage. Methods: A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9(*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9(*2 allele. Results: VKORC1 genotype frequencies were 11{\%}, 24{\%} and 65{\%} for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81{\%} ((*1\(*1), 3.3{\%} ((*1\(*2), 9.7{\%} (*1\(*3), 4.5{\%} ((*2\(*2) and 0.65{\%} (2\(*3 and (*3\(*3). VKORC1 TT and CYP2C9(*2\(*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7{\%} and 15.6{\%} of warfarin dose variability, respectively, and together with clinical factors explained 61.3{\%} of total variability. Conclusion: VKORC1-TT and CYP2C9 (*1/(*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.",
keywords = "CYP2C9, Real-time PCR, VKORC1, Warfarin",
author = "{El Din}, {M. S.} and Amin, {Dalia G.} and Ragab, {S. B.} and Ashour, {E. E.} and Mohamed, {M. H.} and Mohamed, {A. M.}",
year = "2012",
month = "10",
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language = "English",
volume = "34",
pages = "517--524",
journal = "International Journal of Laboratory Hematology",
issn = "1751-5521",
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Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose : Proposal for a new dosing regimen. / El Din, M. S.; Amin, Dalia G.; Ragab, S. B.; Ashour, E. E.; Mohamed, M. H.; Mohamed, A. M.

In: International Journal of Laboratory Hematology, Vol. 34, No. 5, 01.10.2012, p. 517-524.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose

T2 - Proposal for a new dosing regimen

AU - El Din, M. S.

AU - Amin, Dalia G.

AU - Ragab, S. B.

AU - Ashour, E. E.

AU - Mohamed, M. H.

AU - Mohamed, A. M.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Introduction: Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9(*2 and CYP2C9(*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage. Methods: A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9(*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9(*2 allele. Results: VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% ((*1\(*1), 3.3% ((*1\(*2), 9.7% (*1\(*3), 4.5% ((*2\(*2) and 0.65% (2\(*3 and (*3\(*3). VKORC1 TT and CYP2C9(*2\(*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability. Conclusion: VKORC1-TT and CYP2C9 (*1/(*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.

AB - Introduction: Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9(*2 and CYP2C9(*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage. Methods: A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9(*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9(*2 allele. Results: VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% ((*1\(*1), 3.3% ((*1\(*2), 9.7% (*1\(*3), 4.5% ((*2\(*2) and 0.65% (2\(*3 and (*3\(*3). VKORC1 TT and CYP2C9(*2\(*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability. Conclusion: VKORC1-TT and CYP2C9 (*1/(*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.

KW - CYP2C9

KW - Real-time PCR

KW - VKORC1

KW - Warfarin

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U2 - 10.1111/j.1751-553X.2012.01426.x

DO - 10.1111/j.1751-553X.2012.01426.x

M3 - Article

VL - 34

SP - 517

EP - 524

JO - International Journal of Laboratory Hematology

JF - International Journal of Laboratory Hematology

SN - 1751-5521

IS - 5

ER -