Population diversity and the performance of warfarin dosing algorithms

Suarez‐Kurtz, Guilherme

doi:10.1111/j.1365-2125.2011.04018.x

Cited by 20 publications

(21 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The application of warfarin dosing algorithms to different patient cohorts expands on this notion: Botton et al [29] reported a comparatively inferior performance of the algorithm derived by Perini et al [23] when applied to patients exclusively of European ancestry from Porto Alegre, in the south region. By the same token, the algorithms developed by Botton et al [29] did not reproduce in the patients from Rio de Janeiro, the results obtained in the original cohort [30]. These discrepancies may be related to differences in biogeographical ancestry between the two study cohorts, exclusively European in the Porto Alegre study versus admixed European/African/Amerindian in Rio de Janeiro.…”

Section: Future Science Groupmentioning

confidence: 88%

Pharmacogenomic Implications of Population Admixture: Brazil as a Model Case

2014

Self Cite

View full text Add to dashboard Cite

The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color' categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the advantages and challenges of performing pharmacogenomic trials in Brazilians.

show abstract

Section: Future Science Groupmentioning

confidence: 88%

Pharmacogenomic Implications of Population Admixture: Brazil as a Model Case

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 Distinct from Caucasian populations, the frequency of the VKORC1-1639 GG genotype is 0-2%, the GA genotype $18%, and the AA genotype $80% in the Chinese population. 18 The frequency of the CYP2C9*1*1 genotype is reported to be $95%, the *1*3 genotype $5% and the *3*3 genotype 0% (i.e., not present).The *2,*4 and *5 variants have also been reported as being absent in the Chinese population.…”

Section: Discussionmentioning

confidence: 99%

Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients

Jin

Zhang

et al. 2013

J Int Med Res

View full text Add to dashboard Cite

Objective: To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 (VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy. Methods: Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated. Results: Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 AE 0.14) than those with the VKORC1-1639 AG genotype (1.32 AE 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 AE 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 AE 0.70 mg/day). Conclusions: Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.

show abstract

“…Furthermore, the performance of warfarin dosing algorithms in the literature as expressed by correlation coefficient R 2 vary considerably between 0.2 and 0.6, but is consistently superior in Europeans compared with Asians or populations of African decent. 5 This discrepancy may arise owing to the fluctuations in racial definitions, clinal variations, social/lifestyle contexts, population migration and historical perspectives. 20,21 These observations strengthens the notion that warfarin dosing algorithms will be microgeographically defined population-specific.…”

Section: Vkorc1_9041 N (%)mentioning

confidence: 99%

“…5 The inconsistent performance of these dosing algorithms across population groups may reflect significant differences in the contribution of non-genetic factors, including compliance rate or yet to be uncovered additional genetic variants or factors. It implies that performance must be assessed for each study population before making therapeutic decisions, especially for admixed populations.…”

Section: Introductionmentioning

confidence: 99%

“…It implies that performance must be assessed for each study population before making therapeutic decisions, especially for admixed populations. 4,5 Towards this end, we carried out a warfarin pharmacogenetic study, in a microgeographically defined, ethnically admixed Omani patients on warfarin therapy, but sharing among them comparable lifestyle and environmental factors.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients

et al. 2012

View full text Add to dashboard Cite

The objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients. Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1 loci were significantly associated with warfarin dose in the studied patient population. However, multiple regression model showed that only the atrial fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and VKORC1 GA and AA genotypes remained significant. A multivariate model, which included demographic, clinical and pharmacogenetic variables together explained 63% of the overall inter-patient variability in warfarin dose requirement in this microgeographically defined, ethnically admixed Omani patient cohort on warfarin. This locally developed model performed much better than the International Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G4A polymorphism emerged as the single most important predictor of warfarin dose variability, even in this admixed population (partial R 2 ¼ 0.45).

show abstract

Population diversity and the performance of warfarin dosing algorithms

Cited by 20 publications

References 12 publications

Pharmacogenomic Implications of Population Admixture: Brazil as a Model Case

Pharmacogenomic Implications of Population Admixture: Brazil as a Model Case

Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients

Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients

Contact Info

Product

Resources

About