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首页> 外文期刊>Cardiovascular therapeutics >Influence of UDP-Glucuronosyltransferase Polymorphisms on Stable Warfarin Doses in Patients with Mechanical Cardiac Valves
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Influence of UDP-Glucuronosyltransferase Polymorphisms on Stable Warfarin Doses in Patients with Mechanical Cardiac Valves

机译：UDP-葡萄糖醛酸糖基转移酶多态性对机械性心脏瓣膜患者稳定华法林剂量的影响

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Aim: This study aimed to evaluate the effect of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) polymorphisms on warfarin dosing requirements in patients with mechanical cardiac valves. Methods: A total of 191 patients with stable warfarin doses from the EAST Group of Warfarin were included in this study. The influence of genetic polymorphisms on stable warfarin doses was investigated by genotyping 6 single nucleotide polymorphisms (SNPs): vitamin K epoxide reductase complex 1 (VKORC1) rs9934438, cytochrome P450 (CYP) 2C9 rs1057910, CYP4F2 rs2108622, and UGT1A1 (rs887829, rs4148323, and rs4124874). An additional subgroup analysis was carried out using patients with wild-type homozygote carriers of CYP2C9. Results: One UGT1A1 SNP of rs887829 (C>T) exhibited significant association with stable warfarin doses in the study population and subgroup. Patients with the T allele in UGT1A1 rs887829 (CT or TT) required higher doses than those with the CC genotype in the study population (6.32.4mg vs. 5.2 +/- 1.6mg, P=0.003). Similarly, in the subpopulation of AA carriers in the CYP2C9 gene, patients with the T allele required significantly higher doses of warfarin than those with other genotypes of rs887829 (6.5 +/- 2.4 vs. 5.3 +/- 1.5mg, P=0.002). Approximately 45.1% of overall interindividual variability in warfarin dose requirement was explained by the multivariate regression model. VKORC1, CYP2C9, UGT1A1 rs887829, age, and CYP4F2 accounted for 28.2%, 6.6%, 5.5%, 3.0%, and 1.8% of the variability, respectively. Conclusion: Our results suggest that UGT1A1 could be a determinant of stable warfarin doses.
机译：目的：本研究旨在评估机械性心脏瓣膜患者中尿苷二磷酸（UDP）-葡萄糖醛酸转移酶（UGT）多态性对华法林剂量的影响。方法：本研究共纳入了191名来自华法林EAST组的稳定华法林剂量的患者。通过对6种单核苷酸多态性（SNP）进行基因分型，研究了遗传多态性对稳定华法林剂量的影响：维生素K环氧还原酶复合物1（VKORC1）rs9934438，细胞色素P450（CYP）2C9 rs1057910，CYP4F2 rs2108622和UGT1A1（rs887）和rs4124874）。使用具有CYP2C9野生型纯合子携带者的患者进行了其他亚组分析。结果：在研究人群和亚组中，rs887829的一个UGT1A1 SNP（C> T）与稳定的华法林剂量呈显着相关。在研究人群中，UGT1A1 rs887829中的T等位基因患者（CT或TT）比CC基因型患者需要更高的剂量（6.32.4mg对5.2 +/- 1.6mg，P = 0.003）。同样，在CYP2C9基因的AA携带者亚群中，具有T等位基因的患者比其他基因型rs887829的患者需要更高的华法林剂量（6.5 +/- 2.4 vs. 5.3 +/- 1.5mg，P = 0.002） 。多元回归模型解释了华法林剂量需求中整体个体间差异的约45.1％。 VKORC1，CYP2C9，UGT1A1 rs887829，年龄和CYP4F2分别占变异性的28.2％，6.6％，5.5％，3.0％和1.8％。结论：我们的结果表明，UGT1A1可能是稳定的华法林剂量的决定因素。

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