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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.

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

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  • Medientyp: E-Artikel
  • Titel: Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos
  • Beteiligte: 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.
  • Erschienen: Wiley, 2021
  • Erschienen in: Clinical and Translational Science
  • Sprache: Englisch
  • DOI: 10.1111/cts.12854
  • ISSN: 1752-8054; 1752-8062
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>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 (<jats:italic>n </jats:italic>= 411) and Brazil (<jats:italic>n </jats:italic>= 663) were genotyped for <jats:italic>VKORC1</jats:italic> c.‐1639G&gt; A, common <jats:italic>CYP2C9</jats:italic> variants, <jats:italic>CYP4F2*3</jats:italic>, and <jats:italic>NQO1*2</jats:italic>. 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, <jats:italic>VKORC1</jats:italic> and <jats:italic>CYP2C9</jats:italic> variants were associated with lower warfarin dose (β = −0.29, <jats:italic>P </jats:italic>&lt; 2.0 × 10<jats:sup>−16</jats:sup>; β = −0.21, <jats:italic>P</jats:italic> = 4.7 × 10<jats:sup>−7</jats:sup>, respectively) whereas <jats:italic>CYP4F2</jats:italic> and <jats:italic>NQO1</jats:italic> variants were associated with higher dose (β = 0.10, <jats:italic>P</jats:italic> = 2 × 10<jats:sup>−4</jats:sup>; β = 0.10, <jats:italic>P</jats:italic> = 0.01, respectively). Associations with <jats:italic>VKORC1</jats:italic> (β = −0.14, <jats:italic>P</jats:italic> = 2.0 × 10<jats:sup>−16</jats:sup>), <jats:italic>CYP2C9</jats:italic> (β = −0.07, <jats:italic>P</jats:italic> = 5.6 × 10<jats:sup>−10</jats:sup>), and <jats:italic>CYP4F2</jats:italic> (β = 0.03, <jats:italic>P</jats:italic> = 3 × 10<jats:sup>−3</jats:sup>), but not <jats:italic>NQO1*2</jats:italic> (β = 0.01, <jats:italic>P</jats:italic> = 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 <jats:italic>VKORC1</jats:italic>, <jats:italic>CYP2C9</jats:italic>, and <jats:italic>CYP4F2</jats:italic> with warfarin dose in Latinos from the United States and Brazil.</jats:p>
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