Tang X-Y, Zhang J, Peng J, Tan S-L, Zhang W, Song G-B, Liu L-M, Li C-L, Ren H, Zeng L, Liu Z-Q, Chen X-P, Zhou X-M, Zhou H-H, Hu J-X, Li Z
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.
J Clin Pharm Ther. 2017 Aug;42(4):438-445. doi: 10.1111/jcpt.12527. Epub 2017 Apr 21.
Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR).
A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD.
The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (P<.05). But they were ruled out in the multivariate regression analysis. There were no significant differences in the average warfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05).
The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (P<.05), but their contributions were not significant after accounting for other factors. MIR133B rs142410335 makes no significant contributions to warfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses.
华法林是一种广泛使用的抗凝剂，治疗指数较窄。已证实维生素K环氧化物还原酶复合体亚单位1（VKORC1）、细胞色素P450 2C9（CYP2C9）和细胞色素P450 4F2（CYP4F2）基因的多态性与华法林稳定剂量（WSD）相关。是否有其他基因或变异影响剂量尚不清楚。我们研究的目的是调查汉族机械心脏瓣膜置换术（MHVR）患者中γ-谷氨酰羧化酶（GGCX）、miR-133变异与WSD之间的关系。
共纳入231例患者进行研究。采集血样进行基因分型。比较不同GGCX或miR-133基因型患者的平均WSD。进行回归分析以检验基因多态性与WSD之间的任何关联。
GGCX rs699664 TT基因型和rs12714145 TT基因型患者的华法林剂量分别为3.77±0.93（95%CI：3.35 - 4.19）mg/d和3.70±1.00（95%CI：3.32 - 4.09）mg/d。GGCX rs699664和rs12714145基因型与WSD显著相关（P<0.05）。但在多变量回归分析中被排除。MIR133B rs142410335野生型和变异基因型患者的平均华法林稳定剂量无显著差异（P>0.05）。
GGCX rs699644和rs12714145基因型与WSD显著相关（P<0.05），但在考虑其他因素后其作用不显著。在单变量回归和多变量回归分析中，MIR133B rs142410335对汉族MHVR患者的华法林稳定剂量均无显著贡献。
