(P274) DETERMINANTS OF VENOUS THROMBOSIS RISK IN THE HUNGARIAN POPULATION

Background: Venous thrombosis (VT) is a multifactorial trait that contributes to the burden of cardiovascular diseases worldwide. In Europe, although overall CVD-related morbidity is decreasing, mortality is substantially high. Hungary shares the largest burden of this mortality. Although several risk factors provoke the susceptibility of individuals to VT risk, the role of strongly associated VT SNPs (rs6025 (F5 Leiden), rs2066865 (FGG), rs2036914 (F11), rs8176719(ABO), and rs1799963 (F2)) and well known VT risk factors is enormous. Thus, we aimed to identify the extent to which those factors determine VT risk in the Hungarian population.

METHODS AND RESULTS: A case-control study was conducted among 298 clinically confirmed VT cases and 400 healthy controls to determine the VT risk in the Hungarian population. Standard genetic models were used to establish the association between inheritable risk factors and VT disease risk. Sex adjusted odds ratio (AOR) with their respective 95% CI was computed to explore the association between well-known risk factors and VT risk. We also estimate the area under receiver operating characteristic curves (AUCs) value to determine an individual and joint VT risk predictability of both inheritable and uninheritable VT risk factors. Result: The mean age of the VT cases was significantly higher than the control group (63.4±16.4 years vs. 43.8±12.6 years, p< 0.001). The risk of VT is 12.8 times higher among elderly (> 60 years) compared to those aged < 60 years. Besides, the likelihood of VT risk is 2.3 times higher among obese subjects than normal-weight subjects. Leiden mutation (rs6025) is the most prevalent VT risk allele in the Hungarian population (AOR=3.52,95%CI:2.50;4.95). The rs6025 SNP remained significantly associated with VT disease risk using all genetic models after multiple correction testing. However, rs2036914 (AOR=1.38,95% CI:1.11;1.71) and rs8176719 (AOR=1.33,95%CI:1.07;1.64) remained statistically significant only by the multiplicative model. The AUC of Leiden mutation (rs6025) showed better discriminative accuracy than other SNPs (AUC=0.62,95% CI: 0.57; 0.66). Furthermore, the combination of genetic and non-genetic VT risk factors significantly increased the AUC value to 0.89 with statistically significant differences (Z=3.924, p< 0.0001).

Conclusion: Our study revealed that aging, obesity, rs6025, rs2036914, and rs8176719 determine the VT risk in the Hungarian population. The combination of genetic and non-genetic risk factors is the best predictor of VT risk in the study population. Thus, stratification of highly vulnerable individuals based on their genetic profiling and well-known VT risk factors is important for the efficient utilization of preventive and control measures for VT risk.