内皮细胞蛋白 C 受体基因 6936A/G 多态性与深静脉血栓形成的关系。

Relationship between endothelial cell protein C receptor gene 6936A/G polymorphisms and deep venous thrombosis.

机构信息

Department of Vascular Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.

出版信息

Chin Med J (Engl). 2011 Jan;124(1):72-5.

PMID:21362311

Abstract

BACKGROUND

Deep venous thrombosis (DVT) can result in pulmonary embolism, a fatal complication that is due to the dislodgement and movement of a blood clot (thrombus) from a limb into the lungs. Genetic risk factors related to DVT development include mutations in coagulation proteins, especially the endothelial protein C receptor (EPCR), a component of the anticoagulation protein C (PC) pathway. The objective of the present study was to analyze the relationship between the 6936A/G polymorphism in the EPCR gene and the occurrence of DVT.

METHODS

This study involved 65 patients with DVT and 71 age- and gender-matched healthy controls. Peripheral blood samples were collected from all subjects. Plasma levels of soluble EPCR (sEPCR) were measured by enzyme-linked immunosorbent assay. Genomic DNA was extracted and EPCR gene product was amplified by a standard PCR reaction. Gene product bands were sequenced to identify EPCR gene polymorphisms.

RESULTS

In the control group, the level of sEPCR in subjects with 6936AG genotype was significantly higher than that in subjects with 6936AA genotype ((0.97 ± 0.32) pg/ml vs. (0.61 ± 0.24) pg/ml, P < 0.01). Similarly in the DVT group, the level of sEPCR in subjects with the 6936AG were greater than that in subjects with the 6936AA genotype ((0.87 ± 0.21) pg/ml vs. (0.50 ± 0.18) pg/ml, P < 0.01). The sEPCR level in DVT patients was significantly higher than that in healthy controls ((0.68 ± 0.32) pg/ml vs. (0.54 ± 0.22) pg/ml, P < 0.05). The 6936AG genotype frequency in DVT patients was significantly higher than that in healthy controls (P < 0.05). In contrast, the 6936AA genotype frequency in DVT patients was lower than that in healthy controls (P < 0.05). Subjects carrying 6936AG had an increased risk of thrombosis (OR = 2.75, 95%CI: 1.04 - 7.30, P < 0.05).

CONCLUSIONS

EPCR gene 6936A/G polymorphism is associated with increased plasma levels of sEPCR. Subjects carrying 6936AG likely have an increased risk of thrombosis.

摘要

背景

深静脉血栓（DVT）可导致肺栓塞，这是一种致命的并发症，是由于血液凝块（血栓）从肢体脱落并移动到肺部引起的。与 DVT 发展相关的遗传风险因素包括凝血蛋白的突变，尤其是内皮蛋白 C 受体（EPCR），它是抗凝蛋白 C（PC）途径的组成部分。本研究的目的是分析 EPCR 基因 6936A/G 多态性与 DVT 发生之间的关系。

方法

本研究纳入了 65 例 DVT 患者和 71 名年龄和性别匹配的健康对照者。所有受试者均采集外周血样。通过酶联免疫吸附试验测量可溶性 EPCR（sEPCR）的血浆水平。提取基因组 DNA，通过标准 PCR 反应扩增 EPCR 基因产物。对基因产物条带进行测序以鉴定 EPCR 基因多态性。

结果

在对照组中，6936AG 基因型受试者的 sEPCR 水平明显高于 6936AA 基因型受试者（（0.97 ± 0.32）pg/ml 比（0.61 ± 0.24）pg/ml，P < 0.01）。同样在 DVT 组中，6936AG 基因型受试者的 sEPCR 水平大于 6936AA 基因型受试者（（0.87 ± 0.21）pg/ml 比（0.50 ± 0.18）pg/ml，P < 0.01）。DVT 患者的 sEPCR 水平明显高于健康对照组（（0.68 ± 0.32）pg/ml 比（0.54 ± 0.22）pg/ml，P < 0.05）。DVT 患者的 6936AG 基因型频率明显高于健康对照组（P < 0.05）。相比之下，DVT 患者的 6936AA 基因型频率低于健康对照组（P < 0.05）。携带 6936AG 的受试者发生血栓的风险增加（OR = 2.75，95%CI：1.04-7.30，P < 0.05）。