[1]张建军a,靳志雄b,胡常晖c,等.PAI-1 基因多态性与血小板聚集率交互作用对下肢深静脉血栓形成的影响[J].现代检验医学杂志,2023,38(06):48-53.[doi:10.3969/j.issn.1671-7414.2023.06.009]
 ZHANG Jianjuna,JIN Zhixiongb,HU Changhuic,et al.Effect of Interaction between PAI-1 Gene Polymorphism and Platelet Aggregation Rate on Deep Venous Thrombosis of Lower Limbs[J].Journal of Modern Laboratory Medicine,2023,38(06):48-53.[doi:10.3969/j.issn.1671-7414.2023.06.009]
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PAI-1 基因多态性与血小板聚集率交互作用对下肢深静脉血栓形成的影响()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年06期
页码:
48-53
栏目:
论著
出版日期:
2023-11-15

文章信息/Info

Title:
Effect of Interaction between PAI-1 Gene Polymorphism and Platelet Aggregation Rate on Deep Venous Thrombosis of Lower Limbs
文章编号:
1671-7414(2023)06-048-06
作者:
张建军a靳志雄b胡常晖c黄秀萍a
(张家口市第一医院a. 急诊科;b. 普外一科;c. 肾内科,河北张家口 075000)
Author(s):
ZHANG Jianjuna JIN Zhixiongb HU Changhuic HUANG Xiupinga
(a.Department of Emergency; b.the First Department of General Surgery; c. Department of Nephrology, the First Hospital of Zhangjiakou, Hebei Zhangjiakou 075000, China)
关键词:
纤溶酶原激活物抑制剂1 型- 基因多态性血小板聚集率交互作用下肢深静脉血栓
分类号:
R543.6:R446.11
DOI:
10.3969/j.issn.1671-7414.2023.06.009
文献标志码:
A
摘要:
目的 探讨纤溶酶原激活物抑制剂1 型(plasminogen activator inhibitor type 1,PAI-1)基因多态性与血小板聚集率交互作用对下肢深静脉血栓(deep vein thrombosis,DVT)形成的影响。方法 选择2020 年2 月~ 2023 年2 月于张家口市第一医院就诊的下肢DVT 患者80 例为观察组,另选80 例健康者为对照组。比较两组血小板聚集率表达及多重PCR 扩增目标区域后再进行高通量测序PAI-1 基因基因型和等位基因频率。采用多因素Logistic 回归模型分析DVT发生的危险因素,估算PAI-1 基因4G/5G 单核苷酸多态性(single nucleotide polymorphism, SNP)和血小板聚集率与DVT 发病风险的调整比值比(odds ratio,OR)及95% 置信区间(95% confidence interval,95%CI),分析PAI-1 SNP 与血小板聚集率的交互作用。结果 与对照组比较,观察组患者的血小板计数[(189.56±51.27)×1012/L vs(209.16±71.91)×1012/L)] 水平降低;D- 二聚体(0.96±1.27 mg/L vs 0.45±1.26 mg/L)、PAI-1(33.26±10.12 mg/ml vs 15.14±8.56mg/ml)、卧床时间(4.12±1.20 h vs 2.32±0.78 h)和血小板聚集率(55.25%±15.56 % vs 35.75%±16.23 %)水平均升高,差异有统计学意义(t=1.985,2.550,12.227,11.249,7.757,均P < 0.05)。观察组PAI-1 4G/5G 基因型4G4G,4G5G 和5G5G 基因频率分别为41.25%,47.50% 和11.25%,对照组分别为12.50%,67.50% 和20.00%,差异具有统计学意义(χ2=17.045,P < 0.001)。观察组PAI-1 4G/5G 等位基因4G,5G 频率分别为65.00%,35.00%,对照组分别为46.25%,53.75%,差异有统计学意义(χ2=11.394,P < 0.001)。与5G5G 基因型患者相比,基因型4G5G,4G4G 患者的血小板聚集率依次升高(35.25%±12.55% vs 45.78%±13.45% ,56.48%±15.26%),差异有统计学意义(t=4.297,P < 0.001)。PAI-1 4G/5G 位点基因型4G4G(OR=5.248,95%CI:1.787 ~ 17.124)、携带等位基因4G(OR=4.268,95%CI:1.897 ~ 15.252)和血小板聚集(OR=5.514,95%CI:1.815 ~ 21.148)是下肢DVT 的独立危险因素(P<0.05)。PAI-1 4G/5G 位点基因型4G4G 与血小板聚集率在患者下肢DVT 易感性中呈正向交互作用(3.135<1.864×2.024,为次相乘模型)。结论 PAI-1 4G/5G 位点基因型4G4G 和血小板聚集率在患者下肢DVT 易感性中呈正向交互作用且易感性显著增加,应引起临床上重视并早期制定预防措施。
Abstract:
Objective To in vestigate the interaction between plasminogen activator inhibitor type 1 (PAI-1) gene polymorphism and platelet aggregation rate on deep vein thrombosis (DVT) in lower limbs. Methods A total of 80 patients with DVT of lower limbs treated in the First Hospital of Zhangjiakou City from February 2020 to February 2023 were selected as the observation group, and another 80 healthy patients were selected as the control group. The expression of platelet aggregation rate and multiple PCR amplification of the target region were compared between the two groups, followed by high-throughput sequencing of PAI-1 gene genotype and allele frequency. Multivariate Logistic regression model was used to analyze the risk factors of DVT, estimate the adjusted odds ratio (OR) and 95% confidence interval (95%) between 4G/5G SNP and platelet aggregation rate of PAI-1 gene and the risk of DVT. 95%CI to analyze the interaction between PAI-1 SNP and platelet aggregation rate. Results Compared with the control group, the platelet count of observation group [(189.56±51.27) ×1012/L vs (209.16±71.91) ×1012/L)] was decreased, D-dimer (0.96±1.27 mg/L vs 0.45±1.26 mg/L), PAI-1 (33.26±10.12 mg/ml vs 15.14±8.56mg/ml),bed time (4.12±1.20 h vs 2.32±0.78 h) and Platelet aggregation rate (55.25%± 15.56% vs 35.75%± 16.23%) were increased, and the differences were statistically significant (t=1.985,2.550,12.227,11.249,7.757, all P < 0.05). The gene frequencies of PAI-1 4G/5G genotype 4G4G, 4G5G and 5G5G were 41.25%, 47.50% and 11.25% in the observation group and 12.50%, 67.50% and 20.00% in the control group, respectively, and the difference was statistically significant (χ2=17.045, P < 0.001). The frequencies of 4G/5G alleles of PAI-1 in the observation group were 65.00% and 35.00%, respectively, while those in the control group were 46.25% and 53.75%, the difference was statistically significant (χ2=11.394, P < 0.001). Compared with 5G5G genotype patients, platelet aggregation rates in genotype 4G5G and 4G4G patients were increased successively (35.25%±12.55% vs 45.78%±13.45%,56.48%±15.26%), and the difference was statistically significant (t=4.297, P < 0.001). PAI-1 4G/5G locus genotype 4G4G (OR=5.248, 95%CI: 1.787 ~ 17.124), carrier alleles 4G (OR=4.268, 95%CI: 1.897 ~ 15.252) and platelet aggregation (OR=5.514, 95%CI: 1.815 ~ 21.148) were independent risk factors for lower limb DVT (P<0.05). PAI-1 4G/5G site genotype 4G4G had a positive interaction with platelet aggregation rate in patients’ lower limb DVT susceptibility (3.135<1.864×2.024, submultiplication model). Conclusion PAI-1 4G/5G site genotype 4G4G and platelet aggregation rate had a positive interaction in the susceptibility of patients with lower limb DVT, and the susceptibility increased significantly, so clinical attention should be paid to and early prevention measures should be developed.

参考文献/References:

[1] 陶诗友, 洪瑶, 徐德宝. 深静脉血栓低分子肝素治疗中血栓弹力图和凝血指标分析的联合应用[J]. 现代检验医学杂志, 2019, 34( 5): 150-152, 164. TAO Shiyou, HONG Yao, XU Debao. Combined application of thrombelastogram and coagulation analysis in the treatment of deep venous thrombosis with low molecular weight heparin[J]. Journal of Modern Laboratory Medicine, 2019, 34(5): 150-152,164.
[2] SUN Yi, SONG Shenghan. Nonnegligible causes of symptoms of acute lower extremities--3 cases of May-Thurner syndrome with deep vein thrombosis[J].Thrombosis Journal, 2021, 19(1): 25.
[3] NAKAYAMA Y, SATO M, OKAMOTO M, et al. Deep learning-based classification of adequate sonographic images for self-diagnosing deep vein thrombosis[J].PLoS One, 2023, 18(3): e0282747.
[4] SHAH N G, WIBLE B C, PAULISIN J A, et al. Management of inferior vena cava thrombosis with the FlowTriever and ClotTriever systems[J]. Journal of Vascular Surgery-Venous and Lymphatic Disorders,2021, 9(3): 615-620.
[5] 张莹, 程晓东, 胡玉皎, 等. 自身免疫性疾病患者检测PAI-1(4G/5G),ABCB1(3435T>C) 在预防甲强龙治疗发生股骨头坏死风险的应用[J]. 现代检验医学杂志, 2019, 34( 2): 14-16, 19. ZHANG Ying, CHENG Xiaodong, HU Yujiao, et al. Detection of PAI-1(4G/5G)and ABCB1(3435T>C)in patients with autoimmune diseases for the prevention of the risk of femoral head necrosis in the impact therapy of meprednisolone[J]. Journal of Modern Laboratory Medicine, 2019, 34(2): 14-16, 19.
[6] 赵庆忠, 宋卫东, 樊聪慧, 等. 替格瑞洛片联合阿司匹林对急性心肌梗死患者静脉血栓栓塞症发生率、凝血功能及不良反应发生率的影响[J]. 临床和实验医学杂志, 2022, 21( 16): 1704-1708. ZHAO Qingzhong, SONG Weidong, FAN Conghui, et al. Effects of ticagrelor tablets combined with aspirin on the incidence of venous thromboembolism,coagulation and incidence of adverse reactions in patients with acute myocardial infarction[J]. Journal of Clinical and Experimental Medicine, 2022, 21(16): 1704-1708.
[7] WATSON R M, SMITH C B, CRANNAGE E F, et al. Examination of the effectiveness of direct oral anticoagulants in comparison to warfarin in an obese population[J]. Journal of Pharmacy Technology, 2022,38(1): 26-30.
[8] POLCARI K, MILNER R. Management of proximal DVT: clinical benefit of endovenous intervention is still in question[J]. European Journal of Vascular and Endovascular Surgery, 2022, 63(2): 335.
[9] PANDELAKI J, HADIBRATA H, SINI I, et al. Massive DVT from the proximal IVC to the pedal vein:Our approach using aspiration mechanical thrombectomy and open surgery thrombectomy[J]. Radiology Case Reports, 2023, 18(5): 1830-1837.
[10] WANG Ziran, KONG Lingjun, LUO Guoju, et al. Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism[J].Thrombosis Journal, 2022, 20(1): 68.
[11] XIA Xiaoxuan, ZHANG Yexian, WEI Yingying, et al. Statistical methods for disease risk prediction with genotype data[J]. Methods Mol Biol, 2023, 2629: 331-347.
[12] EZAKI M, WADA H, ICHIKAWA Y, et al. Plasma soluble fibrin is useful for the diagnosis of thrombotic diseases[J]. J Clin Med, 2023, 12(7): 2597.
[13] 杨玉芳, 乔瑛. 骨科卧床患者下肢静脉血栓发生的危险因素分析[J]. 血栓与止血学, 2021, 27( 6):1073-1074. YANG Yufang, QIAO Ying. Risk factors of lower extremity venous thrombosis in bedridden orthopedic patients[J]. Chinese Journal of Thrombosis and Hemostasis, 2021, 27(6): 1073-1074.
[14] MENNESSON M, REVEST J M. Glucocorticoid-Responsive tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1): relevance in stress-related psychiatric disorders[J].International Journal of Molecular Sciences, 2023,24(5): 4496.
[15] ELTRINGHAM-SMITH L J, MEIXNER S C,PRYZDIAL E L G, et al. Correction of haemorrhagic shock-associated coagulopathy and impaired haemostasis by plasma, prothrombin complex concentrates or an activated protein C-targeted DNA aptamer in mice[J]. Scientific Reports, 2023, 13(1):3811.
[16] MOYA-SALAZAR J, C?NDOR L Y, ZU?IGA N, et al. Alterations in the coagulation markers did not show differences with the severity of COVID-19 in Peruvian patients: a cross-sectional single-center study[J]. Health Science Reports, 2023, 6(3): e1105.
[17] WILLIAMS G J, CHOWDHURY P, PACKHAM S. Inferior vena cava agenesis: a rare cause of deep vein thrombosis[J]. BMJ case reports, 2022, 15(12):e250511.
[18] LI Jianhong, LIANG Yingna. Associations between mean platelet volume and risk of deep vein thrombosis:a mendelian randomization study and a retrospective study[J]. International Journal of General Medicine,2023, 16: 515-524.
[19] IDING A F J, KREMERS B M M, NAGY M, et al. Translational insights into mechanisms underlying residual venous obstruction and the role of factor XI, P-selectin and GPVI in recurrent venous thromboembolism[J]. Thrombosis Research, 2023, 221:58-64.
[20] KANG Jiaxiang, LIN Wenxiang, WANG Han,et al. Effects of general anesthesia and epidural anesthesia on deep vein thrombosis and perioperative cognitive function of patients undergoing total knee arthroplasty[J]. American Journal of Translational Research, 2022, 14(7): 4786-4794.
[21] CERNERA G, DI MINNO A, AMATO F, et al. Molecular analysis of prothrombotic gene variants in venous thrombosis: a potential role for sex and thrombotic localization[J]. J Clin Med, 2020, 9(4): 1008.
[22] RIERA-DOMINGO C, LEITE-GOMES E,CHARATSIDOU I, et al. Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding[J]. Science Advances,2023, 9(12): eadd5028.

备注/Memo

备注/Memo:
基金项目:河北省医学科学研究课题计划项目(项目编号:20232074):MTHFR 和PAI-1 基因多态性与下肢深静脉血栓形成的关系。
作者简介:张建军(1983-),男,硕士,副主任医师,研究方向:急诊医学,E-mail:qrqdlp@httpnet-163.com.cn。
更新日期/Last Update: 2023-11-15