Genome-wide association study of warfarin maintenance dose in a Brazilian sample.

Academic Article

Abstract

  • 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.
  • Authors

    Published In

  • Pharmacogenomics  Journal
  • Keywords

  • 1000 Genomes Project, Brazilians, CYP2C9, VKORC1, extreme discordant phenotypes, genome-wide association study, warfarin, Aged, Anticoagulants, Brazil, Cytochrome P-450 CYP2C9, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Vitamin K Epoxide Reductases, Warfarin
  • Digital Object Identifier (doi)

    Author List

  • Parra EJ; Botton MR; Perini JA; Krithika S; Bourgeois S; Johnson TA; Tsunoda T; Pirmohamed M; Wadelius M; Limdi NA
  • Start Page

  • 1253
  • End Page

  • 1263
  • Volume

  • 16
  • Issue

  • 11