LRP1 polymorphisms associated with warfarin stable dose in Chinese patients: a stepwise conditional analysis

Pharmacogenomics. 2020 Nov;21(16):1169-1178. doi: 10.2217/pgs-2020-0004. Epub 2020 Oct 23.

Abstract

Aim: The aim of this study was to investigate whether variability in warfarin stable dose (WSD) could be influenced by vitamin K-related polymorphisms in patients with heart valve replacement. Patients & methods: Twenty-nine vitamin K-related SNPs in 208 patients who initially took warfarin and achieved WSD were genotyped. Results: After conducting conditional analysis for both VKORC1 -1639G>A and CYP2C9*3, LRP1 rs1800139 and LRP1 rs1800154 were significantly associated with WSD (p = 0.007 and p = 0.015, respectively). Multivariate analysis showed that LRP1 rs1800139 accounted for 5.9% WSD variability. Conclusion: Our results suggest that a novel vitamin K-related gene, LRP1, exerts a relevant influence on WSD, independent of VKORC1 -1639G>A and CYP2C9*3.

Keywords: LRP1; polymorphisms; stable dose; vitamin K; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Asian People
  • China / epidemiology
  • Cytochrome P-450 CYP2C9 / genetics
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Heart Valve Prosthesis
  • Humans
  • International Normalized Ratio
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide / genetics
  • Vitamin K / genetics
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Vitamin K
  • Warfarin
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases