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

Alrashid, Maryam; Al-Serri, Ahmad; Alshemmari, Salem; Philip, Koshi; Al-Bustan, Suzanne A.

doi:10.1007/s40291-016-0190-7

Cited by 16 publications

(18 citation statements)

References 29 publications

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“…There is scarcity of data to comprehend the patterns of pharmacogenetic variants in the Arab populations. Recent studies reported the distinct occurrence of genetic variants associated with warfarin dosage in Kuwaiti population [3,4]. Other studies described the pharmacogenetic maps of variants associated with warfarin and clopidogrel in Qatari and Omani population [5,6].…”

Section: Introductionmentioning

confidence: 99%

Knowledge, perceptions and confidence of physicians and pharmacists towards pharmacogenetics practice in Kuwait

et al. 2018

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BackgroundPharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An understanding of healthcare providers’ knowledge, perceptions, confidence towards pharmacogenetics, and their active enrollment with pharmacogenetic testing is essential for test acceptance and utilization. This study was designed to assess physicians’ and pharmacists’ knowledge, perceptions, and confidence towards pharmacogenetics, determine the preferred learning format for their future education in pharmacogenetics, and identify the barriers to its application in their practice settings.MethodsA cross-sectional survey was conducted using a pretested self-administered questionnaire on a sample of 629 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis.ResultsThe response rate was 98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics education or training (8.9%), applied pharmacogenetics testing in their practice (9.4%), or provided patient counselling on the results of the pharmacogenetic testing (9.1%), and over 90% of them were physicians. The overall respondents’ mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no significant difference between the physicians and pharmacists scores (p>0.05). Only 16.0% of participants indicated that they felt confident in applying pharmacogenetics in their practice settings. Despite these low levels of knowledge and self-confidence, 70.2% of participants expressed overall positive perceptions towards pharmacogenetics and its clinical implications. These positive overall perceptions were found to be significantly more common among pharmacists compared to physicians (p<0.05). The top two perceived barriers facing the implementation of pharmacogenetics in Kuwait were lack of education or training and clinical guidelines.ConclusionsThese findings highlight important concerns and will aid in the assessment of current pharmacogenetics practice. Also, they will provide further insight in designing future targeted multifaceted interventions to promote the adoption and utilization of pharmacogenetics testing in Kuwait.

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Section: Introductionmentioning

confidence: 99%

Knowledge, perceptions and confidence of physicians and pharmacists towards pharmacogenetics practice in Kuwait

et al. 2018

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“…Kuwaiti and close to Saudi (2%), but lower than in other populations of MENA which were between 6-11%, except for Sudanese where this variant was not detected (73,76,88).…”

Section: Prevalence Of the Studied Genetic Variantsmentioning

confidence: 61%

“…Kuwaiti populations (40%) (66,73,77,88). The CYP2C9*2 MAF was comparable to Saudi, Israeli, Jordanian, Egyptian, Kuwaiti, and Turkish populations which were all between 11-14% (66,72,73,77,78,88,89).…”

Section: Prevalence Of the Studied Genetic Variantsmentioning

confidence: 84%

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

et al. 2019

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Genetic and non-genetic factors were shown to affect warfarin dosing; however, their effect may vary from one population to the other. No previous studies were conducted on the Qatari population to elucidate these factors. Research question: What is the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants in Qataris? and what is their contribution to warfarin dose variability? Study design: An observational cross-sectional study Methods: Hundred and fifty warfarin-treated Qatari patients on a stable dose and a therapeutic INR for at least 3 consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. Results: The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A 0.46, while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one loss of function CYP2C9 allele (*2 or *3) required significantly lower warfarin doses iv compared to non-carriers (24 mg/week vs. 34.1 mg/week, p<0.001). VKORC1 (-1639G>A) and CYP4F2*3 polymorphisms on the other hand were not associated with warfarin dose. Multivariate analysis on the derivation cohort showed that congestive heart failure (CHF) (P=0.002), and CYP2C9*2 & *3 (P<0.001) were associated with lower warfarin dose while smoking (P=0.003) was associated with higher warfarin dose. These factors explained 24.1% of warfarin dose variability in Qatari patients. CYP2C9*2 & *3 variants accounted for 11.8% of warfarin dose variability. In the validation cohort, correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient= 0.41, p=0.005). Conclusion: This study showed that CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with CHF and smoking. Dose reduction should be considered in patients with CHF and those carrying at least one of the CYP2C9*2 & *3 alleles. While dose increase should be considered in smokers. v DEDICATION To my loving family vi ACKNOWLEDGMENTS The completion of this thesis would not have been possible without the kind support and assistance of so many individuals whose names may not all be enumerated. All their efforts and contributions are highly and sincerely appreciated and acknowledged. At foremost, I want to thank GOD for giving me all the strength and good health to complete this work. I would like to extend my gratitude to my family; mom, dad, Aya & Tala, who never seemed to cease their support and reassurance even with distance keeping us apart. My beloved husband, Ammar who always believed in me and stood by my side every step of the way, my son Farouk for always being my source of joy and inspiration. I would like to extend my special thanks and gratitude to my supervisor Dr. Hazem F. Elewa for never being hesitant to share his knowledge and expertise with me, for always supporting and fostering my achievements, and always promoting me to stand out.

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“…However, the study by Alrashid et al [38] was considered of poor quality as there was no reporting of the r 2 value for the dosing model. The sample-size used in some of the studies was less than 100, which is relatively low and may have affected the power of their conclusions [31, 32, 34, 39].…”

Section: Resultsmentioning

confidence: 99%

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

Bader

Elewa

2016

PLoS ONE

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BackgroundWarfarin 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.ObjectiveTo 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.MethodsIn 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.ResultsWe 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 CYP2C9*2 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.ConclusionVariants 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.

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

Cited by 16 publications

References 29 publications

Knowledge, perceptions and confidence of physicians and pharmacists towards pharmacogenetics practice in Kuwait

Knowledge, perceptions and confidence of physicians and pharmacists towards pharmacogenetics practice in Kuwait

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

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