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中国原发性高血压患者中膜联蛋白A5(ANXA5)基因多态性与左心室肥厚(LVH)的相关性

The association between annexin A5 (ANXA5) gene polymorphism and left ventricular hypertrophy (LVH) in Chinese endogenous hypertension patients.

作者信息

Zhang Bei, Zeng Xianchun, Xu Yini, Zhang Yanyan, Huang Niwen, Gu Ying, Shen Xiangchun, Liu Xingde

机构信息

Department of Ultrasound Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang Key Laboratory of Optimal Utilization of Natural Medicinal Resources, School of Pharmaceutical Science, Guizhou Medical University, Guian New District Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University Department of Radiation, Guizhou Provincial People's Hospital Department of Pneumology Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

出版信息

Medicine (Baltimore). 2017 Nov;96(44):e8305. doi: 10.1097/MD.0000000000008305.

Abstract

Left ventricular hypertrophy (LVH) is common in endogenous hypertension (EH). We evaluated annexin A5 (ANXA5) promoter polymorphism in a cross-sectional study with a total of 850 EH patients, including 337 EH patients with LVH.Genotyping of ANXA5 promoter single nucleotide polymorphisms (SNPs) was conducted by SNaPshot assays and statistical analyses were performed to quantify its association with LVH.Of all potential SNPs, rs1050606 showed significant association with LVH (P = .008 in dominant and P = .006 in codominant models, respectively). During further analysis of SNPs on ANXA5 promoter region, rs1050606 had the most prominent effect. Furthermore, haplotypes M2 had higher risk of inducing LVH in EH patients compared with M1 (P = .032, OR = 1.42, 95%CI = 1.03-1.94). Patients with ANXA5 promoter haplotype GATGTC were also more susceptible to LVH (P = .022, OR = 1.35, 95%CI = 1.04-1.74). In the luciferase experiment, ANXA5 rs1050606 had the most promoter activity in myocardial cells (P < .001).These results showed that ANXA5 rs1050606 was significantly associated with LVH in Chinese EH patients, likely via influencing ANXA5 expression in serum and in myocardial cells.

摘要

左心室肥厚(LVH)在内源性高血压(EH)中很常见。我们在一项横断面研究中评估了膜联蛋白A5(ANXA5)启动子多态性,该研究共有850例EH患者,其中包括337例伴有LVH的EH患者。通过SNaPshot分析对ANXA5启动子单核苷酸多态性(SNP)进行基因分型,并进行统计分析以量化其与LVH的关联。在所有潜在的SNP中,rs1050606与LVH显示出显著关联(显性模型中P = 0.008,共显性模型中P = 0.006)。在对ANXA5启动子区域的SNP进行进一步分析时,rs1050606的影响最为显著。此外,与M1相比,单倍型M2在EH患者中诱导LVH的风险更高(P = 0.032,OR = 1.42,95%CI = 1.03 - 1.94)。具有ANXA5启动子单倍型GATGTC的患者也更容易发生LVH(P = 0.022,OR = 1.35,95%CI = 1.04 - 1.74)。在荧光素酶实验中,ANXA5 rs1050606在心肌细胞中具有最强的启动子活性(P < 0.001)。这些结果表明,ANXA5 rs1050606与中国EH患者的LVH显著相关,可能是通过影响血清和心肌细胞中ANXA5的表达来实现的。

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