Abstract
Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06–11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25–28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.
Highlights
Venous thromboembolism (VTE) consists of two related conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE) [1]
Our results suggest that toll-like receptor 9 (TLR9) rs5743836 polymorphism is an independent risk factor for venous thromboembolism (VTE) recurrence in female patients but not in males
No significant difference was observed among recurrent and non-recurrent VTE patients in age, sex, deep vein thrombosis (DVT), 1 3
Summary
Venous thromboembolism (VTE) consists of two related conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE) [1]. Prior epidemiological studies have reported that about half of the patients, which had been diagnosed with VTE, were those who had never been hospitalized nor had any major illness [1, 2]. About two-thirds of the patients diagnosed with symptomatic VTE had DVT and one-third had PE [2]. The mortality rate after 30 days of diagnosis with DVT was reported as 4.6%, with PE as 9.7 and 6.4% for patients diagnosed with VTE (both DVT and PE) [4]. VTE is a chronic disease and patients that have experienced one episode of VTE are always at the risk of recurrence and the risk is highest during the first 6–12 months [5].
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