LRP1 and APOA1 Polymorphisms: Impact on Warfarin International Normalized Ratio-Related Phenotypes.
J Cardiovasc Pharmacol
; 76(1): 71-76, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32282500
ABSTRACT
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 in LRP1 and were found to be correlated with 1-month and 2-month INR variability (P < 0.05). Besides, the APOA1 rs486020 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 of LRP1 and APOA1 gene may play important roles in the variation of warfarin INR-related phenotypes. Our results provide new information for improving warfarin anticoagulation management.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Varfarina
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Coagulação Sanguínea
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Monitoramento de Medicamentos
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Apolipoproteína A-I
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Coeficiente Internacional Normatizado
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Polimorfismo de Nucleotídeo Único
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Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade
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Variantes Farmacogenômicos
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Anticoagulantes
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article