Genome-wide association study of warfarin maintenance dose in a Brazilian sample
| Autor: | Nita A. Limdi, James K. Burmester, Esteban J. Parra, Todd A. Johnson, S. Krithika, Tatsuhiko Tsunoda, Larisa H. Cavallari, Mara H. Hutz, Guilherme Suarez-Kurtz, Mia Wadelius, Mariana R. Botton, Jamila Alessandra Perini, Teri E. Klein, Allan E. Rettie, Julie A. Johnson, Munir Pirmohamed, Stephane Bourgeois |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology medicine.medical_specialty Genotype Genome-wide association study Bioinformatics Polymorphism Single Nucleotide Article Vitamin K Epoxide Reductases Internal medicine Genetics medicine Humans SNP 1000 Genomes Project CYP2C9 Aged Cytochrome P-450 CYP2C9 Pharmacology business.industry Maintenance dose Warfarin Anticoagulants Middle Aged Phenotype Molecular Medicine Female VKORC1 business Brazil Imputation (genetics) Genome-Wide Association Study medicine.drug |
| Zdroj: | Pharmacogenomics. 16:1253-1263 |
| ISSN: | 1744-8042 1462-2416 |
| Popis: | Aim: 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. Original submitted 14 January 2015; Revision submitted 26 May 2015 |
| Databáze: | OpenAIRE |
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