载脂蛋白 F 基因多态性与稳定性冠状动脉疾病中冠状动脉狭窄严重程度的相关性。

Association of TAFI gene polymorphisms with severity of coronary stenosis in stable coronary artery disease.

机构信息

Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.

Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand; Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Thromb Res. 2018 Nov;171:171-176. doi: 10.1016/j.thromres.2018.10.001. Epub 2018 Oct 3.

DOI:10.1016/j.thromres.2018.10.001

PMID:30321704

Abstract

INTRODUCTION

Coronary stenosis is a consequence of atherosclerotic plaque progression that is associated with impaired fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor 1 (PAI-1) are fibrinolysis inhibitors whose levels are influenced by acquired conditions and by polymorphisms. This study therefore aimed to investigate the association of TAFI and PAI-1 gene polymorphisms with severity of coronary stenosis in subjects with stable coronary artery disease (CAD).

MATERIALS AND METHODS

A total of 327 subjects suspected with CAD who underwent a coronary angiogram were recruited. Gensini score was applied to stratify the severity of coronary stenosis. Based on the Gensini score, the subjects were categorized into low-medium (<20) or high (≥20) groups. The study polymorphisms included TAFI Ala147Thr (505G/A), Thr325Ile (1040C/T), +1542C/G, +1583T/A and PAI-1 -675 4G/5G. Most polymorphisms were genotyped by allele-specific polymerase chain reaction, except for TAFI Thr325Ile that was genotyped by polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

A significant increase in the Gensini score was found in TAFI 505A and +1583A allele carriers. Binary regression analysis revealed the independent association of the TAFI 505G/A and +1583T/A polymorphisms with a high Gensini score [adjusted OR = 1.67 (95% CI: 1.03, 2.73) and 1.69 (95% CI: 1.04, 2.76), respectively]. Neither the homozygous PAI-1 -675 4G/4G nor the heterozygous 4G/5G was associated with a high Gensini score.

CONCLUSIONS

The results indicated the contribution of TAFI polymorphisms to atherosclerosis progression and severity of coronary stenosis in stable CAD.

摘要

简介

冠状动脉狭窄是动脉粥样硬化斑块进展的结果，与纤溶受损有关。凝血酶激活的纤溶抑制物（TAFI）和纤溶酶原激活物抑制剂 1（PAI-1）是纤溶抑制剂，其水平受后天条件和多态性的影响。因此，本研究旨在探讨 TAFI 和 PAI-1 基因多态性与稳定型冠心病（CAD）患者冠状动脉狭窄严重程度的关系。

材料和方法

共招募了 327 名疑似 CAD 并接受冠状动脉造影的患者。Gensini 评分用于分层冠状动脉狭窄的严重程度。根据 Gensini 评分，将患者分为低中度（<20）或高度（≥20）组。研究的多态性包括 TAFI Ala147Thr（505G/A）、Thr325Ile（1040C/T）、+1542C/G、+1583T/A 和 PAI-1-6754G/5G。大多数多态性通过等位基因特异性聚合酶链反应进行基因分型，除了 TAFI Thr325Ile 通过聚合酶链反应-限制性片段长度多态性进行基因分型。

结果

TAFI 505A 和 +1583A 等位基因携带者的 Gensini 评分显著升高。二元回归分析显示，TAFI 505G/A 和 +1583T/A 多态性与高 Gensini 评分独立相关[调整后的 OR=1.67（95%CI：1.03，2.73）和 1.69（95%CI：1.04，2.76）]。PAI-1-6754G/4G 纯合子和 4G/5G 杂合子均与高 Gensini 评分无关。