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

Area of Science:

• Pharmacogenomics
• Genetics
• Cardiovascular Medicine

Background:

• Warfarin is a critical anticoagulant for patients with heart valve replacement.
• Warfarin stable dose (WSD) variability poses challenges in clinical management.
• Genetic factors, particularly vitamin K-related polymorphisms, are known to influence WSD.

Purpose of the Study:

• To investigate the influence of vitamin K-related single nucleotide polymorphisms (SNPs) on WSD in patients with heart valve replacement.
• To identify novel genetic markers associated with WSD variability.

Main Methods:

• Genotyping of 29 vitamin K-related SNPs in 208 patients who achieved WSD on warfarin.
• Conditional analysis incorporating VKORC1 -1639G>A and CYP2C9*3.
• Multivariate analysis to assess the contribution of identified SNPs to WSD variability.

Main Results:

• LRP1 rs1800139 and LRP1 rs1800154 SNPs were significantly associated with WSD (p = 0.007 and p = 0.015).
• LRP1 rs1800139 explained 5.9% of the WSD variability.
• The identified LRP1 associations were independent of VKORC1 -1639G>A and CYP2C9*3.

Conclusions:

• The LRP1 gene represents a novel genetic factor influencing WSD.
• LRP1 polymorphisms contribute to warfarin dose variability, offering potential for personalized anticoagulation therapy.
• These findings enhance understanding of the genetic underpinnings of warfarin pharmacogenomics.