期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 76, 期 1, 页码 71-76出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000000834
关键词
warfarin; vitamin K; single-nucleotide polymorphism; INR-related phenotypes; LRP1; APOA1
资金
- Chinese National Science Foundation [81803583]
- National key research and development program [2016YFC0905000, 2016YFC0905001, 2016YFC0905003, 2016YFC1201805]
- Hunan Provincial Natural Science Foundation of China [2017JJ3480]
- Fundamental Research Funds for the Central Universities of Central South University [2018zzts903, 2019zzts803]
Warfarin international normalized ratio (INR)-related phenotypes such as the percentage of INR time in the therapeutic range (PTTR) and INR variability are associated with warfarin adverse reactions. However, INR-related phenotypes greatly vary among patients, and the underlying mechanism remains unclear. As a key cofactor for coagulation proteins, vitamin K can affect warfarin INR values. The aim of this study was to address the influence of vitamin K-related single-nucleotide polymorphisms (SNPs) on warfarin INR-related phenotypes. A total of 262 patients who were new recipients of warfarin therapy and followed up for 3 months were enrolled. Twenty-nine SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass array. Sixteen warfarin INR-related phenotypes were observed. After association analysis, 11 SNPs were significantly associated with at least one INR-related phenotype, and 6 SNPs were associated with at least 2 INR-related phenotypes (P< 0.05). In these SNPs, rs1800139, rs1800154, rs1800141, and rs486020 were the most representative. rs1800139, rs1800154, and rs1800141 locate inLRP1and were found to be correlated with 1-month and 2-month INR variability (P< 0.05). Besides, theAPOA1rs486020 was significantly associated with the first month PTTR (P= 0.009), and patients with C-allele had higher PTTR than those with G-alleles almost during the entire monitoring period. In conclusion, the study revealed that the polymorphisms ofLRP1andAPOA1gene may play important roles in the variation of warfarin INR-related phenotypes. Our results provide new information for improving warfarin anticoagulation management.
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