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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Genetic and nongenetic factors associated with warfarin doserequirements in Egyptian patients
Pharmacogenetics and Genomics, Volume 21, No. 3, Year 2011
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Description
Background and objective: Warfarin is a commonly used oral anticoagulant with a narrow therapeutic index and various genetic and clinical factors that influence interpatient variability in dose requirements. This study investigated the impact of genetic and nongenetic factors on warfarin dose requirements in Egyptians. Methods: DNA was extracted from 207 patients taking warfarin for more than 2 months and genotyped for VKORC1 (3673 G>A), CYP2C9 *2*3*4*5*8, CYP4F2 (V33M; rs2108622), APOE (rs429358, rs7412), and CALU(rs339097) gene polymorphisms. Linear regression modeling was conducted to identify the genetic and nongenetic factors that independently influence warfarin dose requirements. RESULTS: VKORC1 3673 AA or GA genotype (P<0.0001), one or two variant alleles of CYP2C9 gene (P=0.0004), APOE ε2 haplotype (P=0.01), and increasing age (P<0.0001) were all associated with lower warfarin dose, whereas smoking (P=0.025) and pulmonary embolism (P=0.0059) showed association with higher warfarin doses. These factors explained 31% of the warfarin dose variability. This is the first independent confirmation of the association of the CALU rs339097 variant with higher warfarin dose requirement, although inclusion of thissinglenucleotide polymorphism in the multiple regressionmodel failed to achieve significance (P=0.066). CYP4F2 (V33M) polymorphism was not significant (P=0.314), despite itshigh frequency in the studied population (42%). Conclusion: The study shows that VKORC1, CYP2C9 polymorphisms, APOE ε2 variant, and several clinical/demographic variables are important determinants of warfarin dose requirements in Egyptian patients. The percentage of variability explained by these factors is lowerthan in those of European ancestry, but similar tothevariability explained in Asians and African ancestry. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Authors & Co-Authors
Shahin, Mohamed Hossam A.
United States
Departments of Pharmacy Practice and Clinical Pharmacy
Khalifa, Sherief Ibrahim
Qatar, Doha
Qatar University
Gong, Yan
United States, Gainesville
University of Florida
Hammad, Lamiaa N.A.
Egypt, Cairo
Faculty of Pharmacy
Sallam, Mohamed Tarif H.
Egypt, Cairo
Faculty of Medicine - Ain Shams University
El-Shafey, Mostafa M.
Egypt, Cairo
Faculty of Pharmacy
Ali, Shawky S.
Egypt, Cairo
Faculty of Pharmacy
Mohamed, Mohamed Eslam F.
United States, Gainesville
University of Florida
Langaee, Taimour Yousef
United States, Gainesville
University of Florida
Johnson, Julie A.
United States, Gainesville
University of Florida
Statistics
Citations: 97
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1097/FPC.0b013e3283436b86
ISSN:
17446872
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cross Sectional Study