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Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

El Rouby, Nihal ; Rodrigues Marcatto, Leiliane ; Claudio, Karla ; Camargo Tavares, Letícia ; Steiner, Heidi ; Botton, Marianna R. ; Lubitz, Steve A. ; Fallon, Echo N. ; Yee, Kevin ; Kaye, Justin ; Scott, Stuart A. ; Karnes, Jason ; Caleb Junior de Lima Santos, Paulo ; Duconge, Jorge ; Cavallari, Larisa H.

Clinical and translational science, 2021-01, Vol.14 (1), p.268-276 [Periódico revisado por pares]

United States: John Wiley & Sons, Inc

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Título:
Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos
Autor: El Rouby, Nihal ; Rodrigues Marcatto, Leiliane ; Claudio, Karla ; Camargo Tavares, Letícia ; Steiner, Heidi ; Botton, Marianna R. ; Lubitz, Steve A. ; Fallon, Echo N. ; Yee, Kevin ; Kaye, Justin ; Scott, Stuart A. ; Karnes, Jason ; Caleb Junior de Lima Santos, Paulo ; Duconge, Jorge ; Cavallari, Larisa H.
Assuntos: African Americans ; Aged ; Anticoagulants ; Anticoagulants - administration & dosage ; Biological Variation, Population - genetics ; Brazil ; Cohort Studies ; Cytochrome P-450 CYP2C9 - genetics ; Cytochrome P-450 CYP2C9 - metabolism ; Cytochrome P450 Family 4 - genetics ; Cytochrome P450 Family 4 - metabolism ; Data collection ; Deoxyribonucleic acid ; DNA ; Dose-Response Relationship, Drug ; Drug dosages ; Female ; Gene Frequency ; Genotype & phenotype ; Genotypes ; Hispanic Americans ; Hispanic or Latino - genetics ; Hispanic or Latino - statistics & numerical data ; Humans ; Male ; Middle Aged ; Multiple regression analysis ; NAD(P)H Dehydrogenase (Quinone) - genetics ; NAD(P)H Dehydrogenase (Quinone) - metabolism ; Patients ; Pharmacogenomic Testing - statistics & numerical data ; Pharmacogenomic Variants ; Regression analysis ; Thromboembolism - drug therapy ; United States ; Vitamin K Epoxide Reductases - genetics ; Vitamin K Epoxide Reductases - metabolism ; Warfarin ; Warfarin - administration & dosage
É parte de: Clinical and translational science, 2021-01, Vol.14 (1), p.268-276
Notas: These authors jointly supervised the work.
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Descrição: We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.‐1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10−16; β = −0.21, P = 4.7 × 10−7, respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10−4; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10−16), CYP2C9 (β = −0.07, P = 5.6 × 10−10), and CYP4F2 (β = 0.03, P = 3 × 10−3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43–46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin‐treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil.
Editor: United States: John Wiley & Sons, Inc
Idioma: Inglês

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Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

United States: John Wiley & Sons, Inc

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