Ju Shang, Gao Yu, Cao Xin, Zhang Xiao-Fu, Yan Cheng-Cheng, Liu Feng-Tong
Department of Peripheral Vascular, Beijing University of Chinese Medicine Dongzhimen Hospital , Beijing, China .
Genet Test Mol Biomarkers. 2017 Sep;21(9):539-546. doi: 10.1089/gtmb.2017.0090. Epub 2017 Sep 5.
This study explored the association between the CYP2C93/CYP2D610/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose.
Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2.5-3.0 mg. Blood samples were collected to detect the initial and stable international normalized ratio (INR) values. The warfarin maintenance dose was obtained if the INR remained within a range of 2.0-3.0 for 3 consecutive days. The genotype distribution and haplotype analysis of the CYP2C93/CYP2D610/CYP3A5*3 alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) testing and SHEsis software, respectively. Logistic regression analysis was used to analyze the risk and protective factors for LEDVT.
The A/G genotypes, G/G genotypes, and G allele of CYP3A53 in the LEDVT group were observed with increased frequency compared with the control group. The LEDVT group displayed a higher ACG haplotype frequency, and lower ACA and ATA haplotype frequencies than the control group. Age, diabetes, low-density lipoprotein, CYP3A53 and the ACG haplotype were independent risk factors for LEDVT. High-density lipoprotein and the ACA haplotype were independent protective factors for LEDVT. The genotype distributions of the CYP2C93, CYP2D610, and CYP3A5*3 genetic polymorphisms were associated with the warfarin maintenance dose.
The CYP3A53 genetic polymorphism may be an important risk factor for LEDVT. Moreover, CYP2C93, CYP2D610, and CYP3A53 are associated with the warfarin maintenance dose.
本研究探讨CYP2C93/CYP2D610/CYP3A5*3基因多态性与下肢深静脉血栓形成（LEDVT）及华法林维持剂量之间的关联。
将536例术后经病理诊断为LEDVT的患者纳入LEDVT组。同时，选取540例接受手术但无LEDVT的患者作为对照组。患者初始给予华法林剂量为2.5 - 3.0毫克。采集血样检测初始和稳定的国际标准化比值（INR）值。若INR连续3天维持在2.0 - 3.0范围内，则获得华法林维持剂量。分别采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测和SHEsis软件分析CYP2C93/CYP2D610/CYP3A5*3等位基因的基因型分布和单倍型分析。采用逻辑回归分析LEDVT的危险因素和保护因素。
与对照组相比，LEDVT组中CYP3A53的A/G基因型、G/G基因型和G等位基因频率增加。LEDVT组的ACG单倍型频率高于对照组，而ACA和ATA单倍型频率低于对照组。年龄、糖尿病、低密度脂蛋白、CYP3A53和ACG单倍型是LEDVT的独立危险因素。高密度脂蛋白和ACA单倍型是LEDVT的独立保护因素。CYP2C93、CYP2D610和CYP3A5*3基因多态性的基因型分布与华法林维持剂量有关。
CYP3A53基因多态性可能是LEDVT的重要危险因素。此外，CYP2C93、CYP2D610和CYP3A53与华法林维持剂量有关。
