Mairuhu A T A, Setiati T E, Koraka P, Hack C E, Leyte A, Faradz S M H, ten Cate H, Brandjes D P M, Osterhaus A D M E, Reitsma P H, van Gorp E C M
Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
Thromb J. 2005 Nov 7;3:17. doi: 10.1186/1477-9560-3-17.
Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.
A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis.
Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9-23.8], peak value during admission: OR 6.3 [95%CI 1.3-30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue.
These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.
登革病毒感染患者血浆中纤溶酶原激活物抑制剂I型(PAI - 1)浓度较高。PAI - 1基因启动子区域的插入/缺失(4G/5G)多态性是否与PAI - 1血浆浓度升高及登革热死亡相关尚不清楚。因此,我们研究了4G/5G多态性与登革热患者PAI - 1血浆浓度及登革热死亡风险之间的关系。
共纳入印度尼西亚三宝垄卡里阿迪医院临床疑似严重登革病毒感染的194例患者。在入院当天、入院后第1、2和7天以及1个月随访时采集血样。使用夹心ELISA试剂盒测量PAI - 1的血浆浓度。通过等位基因特异性PCR分析确定PAI - 1 4G/5G多态性类型。
入院时PAI - 1浓度及入院期间PAI - 1峰值高于健康对照者测量值。PAI - 1浓度处于最高三分位数的患者生存率明显更差(入院时:比值比4.7 [95%可信区间0.9 - 23.8],入院期间峰值:比值比6.3 [95%可信区间1.3 - 30.8])。未发现PAI - 1 4G/5G多态性与PAI - 1血浆浓度、登革热疾病严重程度及登革热死亡率之间存在关联。
这些数据表明,4G/5G多态性对登革病毒感染患者的PAI - 1浓度无显著影响,且与登革热死亡风险无关。需要探索导致登革热患者PAI - 1血浆浓度变化的其他因素。