Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism.
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.
Department of Clinical Sciences, Center for Primary Health Care Research, Lund University/Skåne University Hospital, Malmö, Sweden. abrar.ahmad@med.lu.se.
Abrar
http://orcid.org/0000-0002-6308-952X
A
Ahmad
Department of Clinical Sciences, Center for Primary Health Care Research, Lund University/Skåne University Hospital, Malmö, Sweden.
Kristina
K
Sundquist
Department of Clinical Sciences, Center for Primary Health Care Research, Lund University/Skåne University Hospital, Malmö, Sweden.
Bengt
B
Zöller
Department of Coagulation Disorders, Skåne University Hospital, Lund University, Malmö, Sweden.
Peter J
PJ
Svensson
Department of Clinical Sciences, Center for Primary Health Care Research, Lund University/Skåne University Hospital, Malmö, Sweden.
Jan
J
Sundquist
Department of Clinical Sciences, Center for Primary Health Care Research, Lund University/Skåne University Hospital, Malmö, Sweden.
Ashfaque A
AA
Memon
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D012727:Sex Characteristics; D012737:Sex Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy
C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
Multivariate analysis; Recurrent VTE; Toll-like receptor