Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Chumnumwat, Supatat; Kong, Yi; Lucksiri, Aroonrut; Nosoongnoen, Wichit; Chindavijak, Busba; Chulavatnatol, Suvatna; Sarapakdi, Ajjima; Nathisuwan, Surakit

doi:10.1111/1755-5922.12315

Cited by 8 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding deviates from the expected pattern and supports further investigation of other VKORC1 polymorphisms that may be more useful, particularly in Asians from different race / ethnic backgrounds. 21 The frequencies of CYP2C9*2 and CYP2C9*3 allele mutations were low but found to be most frequent in the Caucasian cohort, with a lower frequency of these gene mutations detected in the Hispanic population and rarely in the Asian patients. Generally, polymorphism along CYP2C9*2 did not show a statistically significant reduction in ADW dose between the wild-type CC and CT genotypes in the Caucasian and Hispanic cohorts (Table 3); however, nonsignificant trends toward lower doses were observed.…”

Section: Discussionmentioning

confidence: 86%

“…Asians from varied ethnic/racial backgrounds may also possess a different VKORC1 polymorphism from the commonly studied VKORC1 (1639 G>A). 21,27 A number of studies have reported both inter-and intrapopulation differences with regard to VKORC1 and S warfarin sensitivity and pharmacokinetics in different ethnic groups. [28][29][30] Other studies have shown that genotyping for VKORC1, CYP2C9 variants, and other clinical variables explained approximately 30% to 50% of the variation in warfarin dose requirements 2,13,14 ; however, other polymorphisms related to warfarin have not been studied, and a large percentage of the variability still remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…22 Further investigations exploring the usefulness of important clinical variables and selection of more relevant polymorphisms or other candidate genes (eg, NQ01 and other CYP2C9 variants, calumenin, or gamma-glutamyl carboxylase, VKORC1 381) in different ethnicities may help to improve the predictive ability of future warfarin dosing models in minority populations. 2,11,21,23,[25][26][27][28][29][30]…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Pharmacogenetics of Warfarin in a Diverse Patient Population

Mak

Lam²,

Pineda

et al. 2019

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

Introduction: Many warfarin-related genotypes have shown to impact the average daily warfarin (ADW) dose requirements; however, information in non-Caucasian populations is limited. Objectives: To identify the frequencies of 4 warfarin-related gene polymorphisms in an ethnically diverse patient population and to examine their impact with other clinical variables on ADW dose requirements. Methods: Patients were recruited from 2 anticoagulation clinics in the Los Angeles area. Blood samples were collected and genotyped for vitamin K epoxide reductase (VKORC1), CYP2C9*2, CYP2C9*3, and CYP4F2 after informed consent. Charts were reviewed to collect demographic, clinical, and warfarin dosing data. Results: A total of 291 patients were included (120 Caucasians, 127 Hispanics, and 44 Asians). In patients with wild-type genotypes for VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2, the highest warfarin requirement was found in Caucasians, lower in Hispanics, and lowest in Asians. Homozygous VKORC1 variant carriers were detected in 15%, 15%, and 79% in Caucasians, Hispanics, and Asians, respectively. Progressive lowering of ADW doses were associated with each VKORC1 variant in Caucasians and Hispanics, but the results in wild-type/ heterozygote Asians were unclear. CYP2C9 variants were associated with lower ADW doses; frequencies of CYP2C9*2 and CYP2C9*3 mutations were higher in Caucasians than in Hispanics but rare to none in Asians. The frequencies of CYP4F2 variant were similar across all ethnicities, but their impact on warfarin dose requirement were insignificant. Clinical factors such as age, body surface area, history of coronary artery disease, deep vein thrombosis or atrial fibrillation, and concomitant amiodarone or HMG-CoA reductase inhibitors had varying impact on the ADW requirements in the ethnicities studied. Conclusions: Our study demonstrated differences among 3 ethnic groups in terms of ADW dose requirements and the impact of associated clinical variables. The results suggest that a single model for all ethnicities may not provide the best performance in predicting warfarin dose requirements.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacogenetics of Warfarin in a Diverse Patient Population

Mak

Lam²,

Pineda

et al. 2019

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Comparison of Maintenance Dose Predictions by Warfarin Dosing Algorithms Based on Chinese and Western Patients

Deng

Wang

2023

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Warfarin has a long record of safe and effective clinical use, and it remains one of the most commonly prescribed drugs for the prevention and treatment of thromboembolic conditions even in the era of direct oral anticoagulants. To address its large interindividual variability and narrow therapeutic window, the Clinical Pharmacogenetics Implementation Consortium has recommended using pharmacogenetic dosing algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al, to dose warfarin when genotype information is available. In China, dosing algorithms based on local patient populations have been developed and evaluated for predictive accuracy of warfarin maintenance doses. In this study, percentage deviations of doses predicted by 15 Chinese dosing algorithms from that by IWPC and Gage algorithms were systematically evaluated to understand the differences between Chinese and Western algorithms. In general, dose predictions by Chinese dosing algorithms tended to be lower than those predicted by IWPC or Gage algorithms for the most prevalent VKORC1 and CYP2C9 genotypes in the Chinese population. The extent of negative prediction deviation appeared to be largest in the younger age group with smaller body weight. Our findings are consistent with previous reports that Asians have a higher sensitivity to warfarin and require lower doses than Western populations.

show abstract

Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype‐Based Dosing Algorithms

et al. 2020

View full text Add to dashboard Cite

Introduction Warfarin’s narrow therapeutic index and high variability in dosage requirements make dosage selection critical. Genetic factors are known to impact warfarin dosage selection. The Hmong are a unique Asian subpopulation numbering over 278,000 in the United States whose participation in genetics‐based research is virtually nonexistent. The translational significance of early reports of warfarin pharmacogene differences in Hmong has not been evaluated. Objectives (i) To validate previously identified allele frequency differences relevant to warfarin dosing in Hmong versus East Asians and (ii) to compare predicted warfarin sensitivity and maintenance doses between a Hmong population and an East Asian cohort. Method DNA collected from two independent cohorts (n=236 and n=198) of Hmong adults were genotyped for CYP2C9 (*2, *3), VKORC1 (G‐1639A), and CYP4F2 (*3). Allele frequencies between the combined Hmong cohort (n=433) and East Asians (n=1165) from the 2009 International Warfarin Pharmacogenetics Consortium (IWPC) study were compared using a χ2 test. Percentages of Hmong and East Asian participants predicted to be very sensitive to warfarin were compared using a χ2 test, and the predicted mean warfarin maintenance dose was compared with a t test. Results The allele frequencies of CYP2C9*3 in the combined Hmong cohort and CYP4F2*3 in the VIP‐Hmong cohort are significantly different from those in East Asians (18.9% vs 3.0%, p<0.001 and 9.8% vs 22.1%, p<0.001, respectively). Comparing the combined Hmong cohort to the East Asian cohort, the percentage of participants predicted to be very sensitive to warfarin was significantly higher (28% vs 5%, p<0.01) and the mean predicted warfarin maintenance dose was significantly lower (19.8 vs 21.3 mg/week, p<0.001), respectively. Conclusion The unique allele frequencies related to warfarin when combined with nongenetic factors observed in the Hmong translate into clinically relevant differences in predicted maintenance dose requirements for Hmong versus East Asians.

show abstract

Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Abstract: Warfarin PGx-guided dosing algorithms derived from large, mixed population performed comparably to Sangviroon et al algorithm. Certain algorithms should be avoided due to significant dose prediction error.

Cited by 8 publications

References 29 publications

Pharmacogenetics of Warfarin in a Diverse Patient Population

Pharmacogenetics of Warfarin in a Diverse Patient Population

Comparison of Maintenance Dose Predictions by Warfarin Dosing Algorithms Based on Chinese and Western Patients

Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype‐Based Dosing Algorithms

Contact Info

Product

Resources

About