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ADAMTS-13 基因多态性与高血压性心房颤动的相关性分析。

Correlation analysis between ADAMTS-13 gene polymorphism and hypertension-induced atrial fibrillation.

机构信息

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2674-2682. doi: 10.26355/eurrev_202003_20537.

DOI:10.26355/eurrev_202003_20537
PMID:32196618
Abstract

OBJECTIVE

The aim of this study was to explore the relationships between ADAMTS-13 gene polymorphisms and hypertension-induced atrial fibrillation (AF).

PATIENTS AND METHODS

A total of 200 hypertensive patients without AF (hypertension group) and 200 hypertensive patients with AF (AF group) treated in our hospital were enrolled. Then, peripheral blood was drawn from these subjects enrolled, and the genomic deoxyribonucleic acids (DNAs) were extracted for analysis of ADAMTS-13 gene polymorphism. Next, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) was employed to determine the expression of ADAMTS-13 gene, and the correlations of ADAMTS-13 gene polymorphism with ADAMTS-13 gene expression and clinical indicators were analyzed.

RESULTS

Results revealed that there was a difference in the distribution of alleles of ADSMTS-13 rs3094374 (p=0.046) and rs34054981 (p=0.039) between AF group and hypertension group. The frequency of T allele of the locus rs3094374 and that of the locus rs34054981 in ADSMTS-13 gene was higher in AF group than that in hypertension group. The distribution of genotypes of ADSMTS-13 rs28503257 (p=0.047) and rs34054981 (p=0.013) in AF group were different from those in hypertension group, and AF group had lower frequency of GA genotype of ADAMTS-13 rs28503257 and higher frequency of CT genotype of ADAMTS-13 rs34054981 than hypertension group. Besides, a difference was found in the distribution of ADSMTS-13 rs3094374 between AF group and hypertension group in recessive model (p=0.043), and the frequency of TC + CC was higher in the recessive model. Moreover, the distribution of the haplotypes CAT (p=0.012) and CGT (p=0.031) in ADAMTS-13 gene showed a difference between AF group and hypertension group. The linkage disequilibrium of the loci rs3094374 and rs28503257 in ADAMTS-13 gene was relatively great (D'=0.293). In addition, the polymorphism of the locus rs34054981 in ADAMTS-13 gene had an association with ADAMTS-13 gene expression (p<0.05). The expression of ADAMTS-13 gene was lower in patients carrying genotype TT in AF group. Furthermore, the ADAMTS-13 rs3094374 polymorphism was related to international normalized ratio (INR) (p=0.034), and the ADAMTS-13 rs28503257 polymorphism was correlated with the levels of brain natriuretic peptide (BNP) (p=0.047) and D-dimer (p=0.033).

CONCLUSIONS

ADAMTS-13 gene polymorphism is correlated with the susceptibility and procession of hypertension-induced AF.

摘要

目的

本研究旨在探讨 ADAMTS-13 基因多态性与高血压诱导的心房颤动(AF)之间的关系。

方法

选取我院收治的 200 例无 AF 的高血压患者(高血压组)和 200 例高血压合并 AF 患者(AF 组)作为研究对象。抽取这些研究对象的外周血,提取基因组脱氧核糖核酸(DNA)进行 ADAMTS-13 基因多态性分析。然后,采用逆转录-定量聚合酶链反应(RT-qPCR)测定 ADAMTS-13 基因的表达,分析 ADAMTS-13 基因多态性与 ADAMTS-13 基因表达及临床指标的相关性。

结果

结果显示,AF 组和高血压组 ADAMTS-13 rs3094374(p=0.046)和 rs34054981(p=0.039)等位基因分布存在差异。ADAMTS-13 基因 rs3094374 位点 T 等位基因频率和 rs34054981 位点的频率在 AF 组中均高于高血压组。ADAMTS-13 rs28503257(p=0.047)和 rs34054981(p=0.013)的基因型在 AF 组中的分布与高血压组不同,AF 组 ADAMTS-13 rs28503257 的 GA 基因型频率较低,ADAMTS-13 rs34054981 的 CT 基因型频率较高。此外,ADAMTS-13 rs3094374 在 AF 组和高血压组的隐性模型中存在分布差异(p=0.043),TC+CC 频率较高。此外,ADAMTS-13 基因的 CAT(p=0.012)和 CGT(p=0.031)单倍型分布在 AF 组和高血压组之间存在差异。ADAMTS-13 基因 rs3094374 和 rs28503257 位点之间存在较强的连锁不平衡(D'=0.293)。此外,ADAMTS-13 基因 rs34054981 多态性与 ADAMTS-13 基因表达有关(p<0.05)。AF 组中携带 TT 基因型的患者 ADAMTS-13 基因表达水平较低。此外,ADAMTS-13 rs3094374 多态性与国际标准化比值(INR)相关(p=0.034),ADAMTS-13 rs28503257 多态性与脑钠肽(BNP)水平(p=0.047)和 D-二聚体(p=0.033)相关。

结论

ADAMTS-13 基因多态性与高血压诱导的 AF 的易感性和进程有关。

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