In:
Clinical and Translational Science, Wiley, Vol. 12, No. 3 ( 2019-05), p. 312-320
Abstract:
Alaska Native and American Indian ( AN / AI ) people have unique pharmacogene variation that may affect warfarin disposition and therapeutic response. We performed targeted genotyping for cytochrome P450 ( CYP ) 2C9 , vitamin K epoxide oxidase reductase complex subunit 1 ( VKORC 1 ), CYP 4F2 , CYP 4F11 , and gamma‐glutamyl carboxylase ( GGCX ) variants in AN / AI people receiving warfarin. The primary outcome was stable warfarin dose, defined as one dose, and associated international normalized ratio within the target range, at least 6 months after starting therapy, with two matching doses at least 2 weeks apart. Genotype–phenotype relationships were assessed by multivariate regression analysis, adjusted for self‐reported heritage, age, gender, and concurrent statin use. VKORC 1 genotype explained 34% of dose variability, with VKORC 1 −1639G 〉 A and 1173C 〉 T associated with a 1.7 mg/day ( P = 1.4e‐05) dose reduction. Additionally, CYP 2C9 N218I was suggestively significant ( P = 0.077), with heterozygotes requiring 1.1 mg/day less than reference individuals. Self‐reported heritage was significantly associated with dose, largely driven by differences in the diagnostic VKORC 1 allele frequencies among AN / AI people.
Type of Medium:
Online Resource
ISSN:
1752-8054
,
1752-8062
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2433157-0
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