Development of a Pharmacogenetic-Guided Warfarin Dosing Algorithm for Puerto Rican Patients

Ramos, Alga S; Seip, Richard L.; Rivera-Miranda, Giselle; Felici-Giovanini, Marcos E; Garcia-Berdecia, Rafael; Alejandro-Cowan, Yirelia; Kocherla, Mohan; Cruz, Iadelisse; Feliu, Juan F.; Cadilla, Carmen L.; Renta, Jessica Y.; Gorowski, Krystyna; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

doi:10.2217/pgs.12.171

Cited by 27 publications

(48 citation statements)

References 45 publications

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“…A genotype‐guided algorithm developed in Brazilian patients with a high percentage of European ancestry more accurately explained warfarin dose variability in this population than the IWPC algorithm ( R 2 = 63% vs R 2 = 46%) (Table ) . In Puerto Rican populations, the warfarin dose variability predicted using European‐derived dosing algorithms is substantially higher ( R 2 = 67%) (Table ) . A tailored algorithm for Puerto Rican patients also performed better than the IWPC algorithm ( R 2 = 67% vs R 2 = 36%) (Table ) .…”

Section: Genotype‐guided Warfarin Dosing Algorithms In Diverse Populamentioning

confidence: 99%

“…The rich genetic diversity of the Latino population makes generalizations regarding the presence and frequency of variants difficult. The majority of published studies have been performed in either Mexican or Caribbean Latinos . In contrast to AAs, MAFs of variants affecting warfarin dose requirements in Latinos are similar to MAFs in populations of European ancestry (Table ) .…”

Section: Identification Of Warfarin Pharmacogenomic Variants In Divermentioning

confidence: 99%

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Warfarin Pharmacogenomics in Diverse Populations

et al. 2017

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Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarinrelated adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.

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Section: Genotype‐guided Warfarin Dosing Algorithms In Diverse Populamentioning

confidence: 99%

Section: Identification Of Warfarin Pharmacogenomic Variants In Divermentioning

confidence: 99%

Warfarin Pharmacogenomics in Diverse Populations

et al. 2017

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“…These algorithms include the clinically actionable CYP2C9 and VKORC1 polymorphisms commonly interrogated in other populations (e.g., CYP2C9*2 , *3 and VKORC1 -1639G>A) [48, 52, 116]. …”

Section: Phase II Metabolizing Enzymes: N-acetyl Transferasesmentioning

confidence: 99%

“…The algorithm for warfarin dose prediction in Puerto Ricans explained two-thirds ( R 2 =0.68) of variability in dose requirements and provided better dose estimations than the clinical algorithms did [52]. In addition, a pharmacogenetic algorithm for 3-day initial dosing that includes genotypes, admixture, and clinical covariates explained 48% of the dose variability in Puerto Ricans.…”

Section: Phase II Metabolizing Enzymes: N-acetyl Transferasesmentioning

confidence: 99%

Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

Claudio‐Campos

Duconge

Cadilla

et al. 2014

Drug Metabolism and Personalized Therapy

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Although the Hispanic population is continuously growing in the United States, they are underrepresented in pharmacogenetic studies. This review addresses the need for compiling available pharmacogenetic data in US Hispanics, discussing the prevalence of clinically relevant polymorphisms in pharmacogenes encoding for drug-metabolizing enzymes. CYP3A5*3 (0.245–0.867) showed the largest frequency in a US Hispanic population. A higher prevalence of CYP2C9*3, CYP2C19*4, and UGT2B7 IVS1+985 A>Gwas observed in US Hispanic vs. non-Hispanic populations. We found interethnic and intraethnic variability in frequencies of genetic polymorphisms for metabolizing enzymes, which highlights the need to define the ancestries of participants in pharmacogenetic studies. New approaches should be integrated in experimental designs to gain knowledge about the clinical relevance of the unique combination of genetic variants occurring in this admixed population. Ethnic subgroups in the US Hispanic population may harbor variants that might be part of multiple causative loci or in linkage-disequilibrium with functional variants. Pharmacogenetic studies in Hispanics should not be limited to ascertain commonly studied polymorphisms that were originally identified in their parental populations. The success of the Personalized Medicine paradigm will depend on recognizing genetic diversity between and within US Hispanics and the uniqueness of their genetic backgrounds.

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“…Cardiovascular ranked second with Puerto Rico [25][26][27][62][63][64] and Costa Rica [11,15,16,50,60,65,113] as the main contributors. Neurology/psychiatry placed third with a greater contribution of the Caribbean islands of Curaçao [85,86,110], Martinique [87], Jamaica [56,61], Cuba [82] and Puerto Rico [35,36,66,95] (Figure 3).…”

Section: Pharmacogenetic Research In Central America and The Caribbean mentioning

confidence: 99%

Pharmacogenetic Research Activity in Central America and the Caribbean: A Systematic Review

et al. 2016

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Aim: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean. Materials & methods: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including ‘phenotyping probe drugs’ for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients). Results: The country with the most intensive pharmacogenetic research was Costa Rica. The most studied medical therapeutic area was oncology, and the most investigated biomarkers were CYP2D6 and HLA-A/B. Conclusion: Research activity on pharmacogenetics in Central American and the Caribbean populations is limited or absent. Therefore, strategies to promote effective collaborations, and foster interregional initiatives and research efforts among countries from the region could help for the rational clinical implementation of pharmacogenetics and personalized medicine.

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Development of a Pharmacogenetic-Guided Warfarin Dosing Algorithm for Puerto Rican Patients

Cited by 27 publications

References 45 publications

Warfarin Pharmacogenomics in Diverse Populations

Warfarin Pharmacogenomics in Diverse Populations

Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

Pharmacogenetic Research Activity in Central America and the Caribbean: A Systematic Review

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