Analysis of Genetic Risk Factors for VTE recurrence: Genotyping in Malmö Thrombophilia Study

Abstract

Venous thromboembolism (VTE) is a health condition that forms clots in the body, ranking among the three most common diseases that cause death. Anticoagulants are prescribed as a therapy for three to six months, depending on the patient’s risk factors. However, some incidents of VTE are described as unprovoked, where there is no risk factor. In these cases, it is assumed that there is a genetic predisposition, and patients are not treated prolonged.
To accurately predict the duration of the anticoagulant therapy, eliminating recurrence, this study aimed to investigate 10 SNPs in VTE-related proteins. In detail, 1,465 Swedish patients participated in a prospective study called Malmö Thrombophilia Study (MATS), and from these, 1,311 were included in this research. Through genotyping, their DNA samples were analyzed for the following SNPs: rs1063856 in the von Willebrand factor (VWF) gene, rs1800291 in Factor VIII (F8), rs710446 in Kininogen 1 (KNG1), rs780094 in Glucokinase Regulatory Protein (GCKR), rs6048 in Factor IX (F9), rs11556218 in Interleukin-16 (IL16), rs11591147 in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), rs34097149 in Probable G-protein Coupled Receptor 149/Neprilysin (GPR149/MME), rs73149254 in GATA Binding Protein 5 (GATA5), and rs72844599 in Thrombospondin Type 1 Domain Containing 7B (THSD7B).
The genotyped results were then statistically analyzed for recurrence association. After Cox regression analysis, most of the single-nucleotide polymorphisms (SNPs) were not related to VTE recurrence. However, KNG1 rs710446 and PCSK9 rs11591147 showed an increased recurrence risk in both univariate and multivariate analyses. Specifically, regarding KNG1 rs710446 in multivariate analyses, the results showed a Hazard ratio of 1.62 (95% CI: 1.04-2.51, p = 0.031). Furthermore, PCSK9 rs11591147 showed in the total cohort a Hazard ratio of 3.40 (95% CI: 1.57-7.36, p = 0.002), while in unprovoked cases, the HR was 3.75 (95% CI: 1.50-9.37, p = 0.005) after multivariate adjustment. Interestingly, PCSK9 showed an association with VTE recurrence in unprovoked cases for the first time in this research.
In conclusion, despite the fact that there were no statistically significant associations observed for most of the polymorphisms, KNG1 rs710446 and PCSK9 rs11591147 were significantly related to VTE recurrence.

Popular Abstract

Can Our Genes Predict Dangerous Blood Clots Returning?
Blood clots in the veins, known as venous thromboembolism (VTE), can become life-threatening. Patients are treated with blood-thinning medication to prevent new clots, but the treatment itself increases the risk of bleeding. One of the biggest challenges for doctors is predicting which patients need longer treatment to spot the clots from returning. This study investigates whether genetic differences can help explain why some patients experience recurrent VTE.
Nearly half of all blood clot cases occur without a clear cause, suggesting that genetics may play an important role. Scientists believe that small changes in DNA, known as genetic mutations, can affect how certain proteins function in the body. Some of these proteins help control blood clotting, while others influence inflammation and blood flow. When these systems do not work properly, the risk of developing dangerous clots may increase.
In this project, ten genetic variants linked to proteins involved in blood clotting were investigated. Some of these proteins directly help the body stop bleeding after an injury, while others influence processes connected to clot formation indirectly. By analyzing DNA samples from patients with VTE, the study explored whether these genetic differences were associated with a higher risk of developing new blood clots after the treatment.
The study included DNA samples from more than 1.300 Swedish patients participating in the Malmö Thrombophilia Study. No clear connection was shown to recurrent VTE, after analyzing most of the genetic variants. However two genetic variants did show a significant association.
One variant was linked to a higher risk of recurrence in patients whose first clot had been triggered by factors such as surgery or immobilization. Another variant showed a string association with recurrent VTE in patients whose blood clots occurred without a clear cause.
These findings suggest that genetics may help explain why some patients develop blood clots repeatedly, even after treatment. In the future, genetic screening could support doctors in deciding which patients may benefit from longer anticoagulant and closer follow-up care.

• author: Skarpelou, Eleni
• supervisor: Nélida Leiva Eriksson; Ashfaque Memon
• organization: Applied Microbiology; Biotechnology; Biotechnology (MSc)
• course: KMBM01 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: biotechnology, genotype, recurrence, single nucleotide polymorphisms (SNP)
• language: English
• id: 9241119
• date added to LUP: 2026-08-11 09:20:39
• date last changed: 2026-08-11 09:20:39