Pharmacogenomics of Warfarin dose requirements in Hispanics☆

Cavallari, Larisa H.; Momary, Kathryn M.; Patel, SR; Shapiro, Nancy L.; Nutescu, Edith A.; Viana, Marlos A. G.

doi:10.1016/j.bcmd.2010.11.005

Cited by 35 publications

(42 citation statements)

References 25 publications

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“…On one hand, CYP2C9 allele frequencies suggest that 92% of natives would show an extensive metabolism, 3% an intermediate metabolism, and apparently poor metabolizers may be absent. (Cavallari et al, 2010). For the heterozygous alleles CYP2C9*2/*3/*5 we listed a higher proportion of GG TT CT CC GG GT TT CC GC GG CC CT TT CC CT TT AA CYP2C9 intermediate metabolizers than previous reports and the frequency of these alleles were significantly higher than in Puerto Ricans, also considered Hispanics (Duconge et al, 2009).…”

Section: Discussionmentioning

confidence: 68%

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

Villegas-Torres

Sanchez-Giron²,

Jaramillo-Villafuerte³

et al. 2015

Gene

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Section: Discussionmentioning

confidence: 68%

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

Villegas-Torres

Sanchez-Giron²,

Jaramillo-Villafuerte³

et al. 2015

Gene

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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%

“…Another study by Cavallari et al [48] investigated the performance of pharmacogenetic-driven dosing algorithms in 50 US Hispanics from Chicago, most of whom were of Mexican descent. The authors developed a pharmacogenetic regression model to predict warfarin dosing in the study population and found that patients with CYP2C9*2 or *3 required 42% less of the warfarin dose than noncarriers did.…”

Section: Phase II Metabolizing Enzymes: N-acetyl Transferasesmentioning

confidence: 99%

“…Polymorphisms in CYP2C9 and VKORC1 explained 55% of the interpatient variability in warfarin dose among Hispanics. Their Hispanic cohort had a similar prevalence of CYP2C9 and VKORC1 alleles when compared to European Caucasians, which explains the effectiveness of previously published dosing algorithms [48]. On the other hand, the Clarification of Optimal Anticoagulation Through Genetics trial selected a group of 65 Hispanics among the studied cohort to compare the pharmacogenetic vs. clinical algorithms, but the data analysis of this subgroup was not performed separately from other studied populations [5].…”

Section: Phase II Metabolizing Enzymes: N-acetyl Transferasesmentioning

confidence: 99%

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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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“…37 Additional studies are needed to identify predictors that may differentially influence warfarin response in these race groups. Moreover, it is likely that incorporation of other genetic 13,38,39 and clinical factors, not assessed in this study, may further improve dose prediction and alter the effect sizes of the predictors evaluated herein.…”

Section: 14mentioning

confidence: 99%

Race influences warfarin dose changes associated with genetic factors

Limdi¹,

Brown

Yan

et al. 2015

Blood

103

111

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• The influence of known genetic variants on warfarin dose differs by race.• Race-specific pharmacogenetic algorithms, rather than race-adjusted algorithms, should be used to guide warfarin dosing.Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P 5 .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P 5 .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race. (Blood. 2015;126(4):539-545)

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Pharmacogenomics of Warfarin dose requirements in Hispanics☆

Cited by 35 publications

References 25 publications

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

Race influences warfarin dose changes associated with genetic factors

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