Genetic Variations Associated With Recurrent Venous Thrombosis

Abstract

Background— The prediction of recurrent venous thrombosis using individual genetic risk predictors has proven to be challenging. The aim of this study was to assess whether multiple genetic single nucleotide polymorphism (SNP) analysis would predict recurrent venous thrombosis. Methods and Results— Patients with a first venous thrombosis were followed for a recurrent venous thrombosis up to 2009 (MEGA follow-up study), which occurred in 608 out of 4100 patients (2.7%/year). Thirty-one common thrombosis-associated single nucleotide polymorphisms (SNPs) were associated with the risk of recurrence. A genetic risk score (GRS) for each individual was calculated by summing the number of risk-increasing alleles for each of the 31 SNPs and for a simplified model consisting of 5 SNPs: rs6025, rs1799963, rs8176719, rs2066865, and rs2036914. The risk of recurrence associated with the GRS was calculated continuously and after stratification in a low and high score. All individual SNPs were at most mildly associated with recurrence risk. Regarding the 31-SNP GRS, recurrence risk was highest in patients with ≥31 and lowest in patients with <21 risk alleles. The discriminative power of the 5-SNP GRS was similar to that of the 31-SNP GRS. The 6-year cumulative incidence of recurrence was high for individuals with ≥5 (20.3%; 95% confidence interval, 16.5–24.1) and low for individuals with ≤1 (9.4%; 95% confidence interval, 6.7–12.1) risk alleles. Predictive power improved after stratification into provoked and unprovoked first events and sex. Conclusions— Multiple genetic SNP analysis is useful in the prediction of recurrent thrombosis, even more so when combining this model with clinical risk factors.

Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner

“…Our results, at least partially, explain that FVL alone may not be a strong contributing factor for VTE recurrence; however, in combination with other risk factors it can better predict the risk of VTE recurrence. These results are in agreement with previous findings showing that FVL is not a strong risk factor for VTE recurrence [38,39].…”

“…Suggesting that combined analysis of these polymorphisms and FVL may better predict VTE recurrence. Recurrent VTE is a multifactorial disease and combination of multiple genetic risk factors has been shown to better predict recurrence compared to presence of individual genetic risk factors [38]. Our results, at least partially, explain that FVL alone may not be a strong contributing factor for VTE recurrence; however, in combination with other risk factors it can better predict the risk of VTE recurrence.…”

Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism

“…Previously, there was a single study in which this polymorphism has been studied for its role in primary deep vein thrombosis (DVT) and no association was found between TLR9 rs5743836 polymorphism and risk of DVT among a European population [27]. Recent studies have suggested that the risk factors for primary and recurrent VTE may differ [37, 38]. Furthermore, the above-mentioned study [27] included only male patients, while our results suggest that TLR 9 rs5743836 polymorphism is only associated with risk of VTE recurrence in female patients but not in male patients.…”

COVID-19 — Toward a comprehensive understanding of the disease

“…Moreover, there are confirmed genetic determinants of deep venous throbosis. Inherited protein C, S, von Willebrand factor, and antithrombin deficiencies include specific single nucleotide polymorphisms and haplotypes [73][74][75][76][77][78][79]. The role of inherited thrombophilic disorders in the risk of severe COVID-19 has not as yet been emphasized or investigated to date.…”