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AuthorBader, Loulia Akram
AuthorElewa, Hazem
Available date2021-03-25T11:33:36Z
Publication Date2016
Publication NamePLoS ONE
ResourceScopus
URIhttp://dx.doi.org/10.1371/journal.pone.0168732
URIhttp://hdl.handle.net/10576/18013
AbstractBackground Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing. Objective To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose. Methods In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews. Results We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C92 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients. Conclusion Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.
Languageen
PublisherPublic Library of Science
Subjectcytochrome P450 2C9
warfarin
CYP2C9 protein, human
cytochrome P450 2C9
vitamin K epoxide reductase
VKORC1 protein, human
warfarin
case control study
case study
cohort analysis
cross-sectional study
CYP2C9 gene
Egyptian
gene
gene frequency
gene sequence
genetic variability
human
Iranian people
Israeli
Kuwaiti
Lebanese
observational study
Omani
prediction
prevalence
prospective study
randomized controlled trial (topic)
Review
single nucleotide polymorphism
Sudanese
systematic review
Turk (people)
VKORC1 gene
Africa
female
genetic variation
genetics
male
metabolism
Middle East
pharmacogenetic testing
Africa, Northern
Cytochrome P-450 CYP2C9
Female
Genetic Variation
Humans
Male
Middle East
Pharmacogenomic Testing
Vitamin K Epoxide Reductases
Warfarin
TitleThe impact of genetic and non-genetic factors on warfarin dose prediction in MENA region: A systematic review
TypeArticle Review
Issue Number12
Volume Number11
dc.accessType Abstract Only


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