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Genome-wide association study of warfarin maintenance dose in a Brazilian sample
journal contribution
posted on 2023-07-26, 15:04 authored by Esteban J. Parra, Mariana R. Botton, Jamila A. Perini, S. Krithika, Stephane Bourgeois, Todd A. Johnson, Tatsuhiko Tsunoda, Munir Pirmohamed, Mia Wadelius, Nita A. Limdi, Larisa H. Cavallari, James K. Burmester, Allan E. Rettie, Teri E. Klein, Julie A. Johnson, Mara H. Hutz, Guilherme Suarez-KurtzAim: Extreme discordant phenotype and genome-wide association (GWA) approaches were combined to explore the role of genetic variants on warfarin dose requirement in Brazilians. Methods: Patients receiving low (≤20 mg/week; n = 180) or high stable warfarin doses (≥42.5 mg/week; n = 187) were genotyped with Affymetrix Axiom® Biobank arrays. Imputation was carried out using data from the combined 1000 Genomes project. Results: Genome-wide signals (p ≤ 5 × 10-8) were identified in the well-known VKORC1 (lead SNP, rs749671; OR: 20.4; p = 1.08 × 10-33) and CYP2C9 (lead SNP, rs9332238, OR: 6.8 and p = 4.4 × 10-13) regions. The rs9332238 polymorphism is in virtually perfect LD with CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). No other genome-wide significant regions were identified in the study. Conclusion: We confirmed the important role of VKORC1 and CYP2C9 polymorphisms in warfarin dose.
History
Refereed
- Yes
Volume
16Issue number
11Page range
1253-1263Publication title
PharmacogenomicsISSN
1744-8042External DOI
Publisher
Future MedicineLanguage
- other