The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions
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ABSTRACT:
SUBMITTER: Natae S
PROVIDER: S-EPMC8576195 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:GxE interaction and VTE risk in the Hungarian population
| PRJEB47437 | ENA
Project description:Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We use multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, to identify Complement Factor H Related Protein 5 (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
2023-03-25 | PXD040913 | Pride
Project description:Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism, and a combination of environmental and genetic risk factors contributes to VTE risk. Within environmental risk factors, some are provoking (e.g., cancer, surgery, trauma or fracture, immobilization, pregnancy and the postpartum period, long-distance travel, hospitalization, catheterization, and acute infection) and others are nonprovoking (e.g., age, sex, race/ethnicity, body mass index and obesity, oral contraceptive or hormone therapy use, corticosteroid use, statin use, diet, physical activity, sedentary time, and air pollution). Additionally, VTE has a strong genetic basis, with approximately 50 to 60% of the variance in VTE incidence attributed to genetic effects. Some genetic susceptibility variants that contribute to risk have been identified in candidate genes, mostly related to the clotting system and responsible for inherited hypercoagulable states (e.g., factor V Leiden, prothrombin, fibrinogen gamma, or blood group non-O). Other susceptibility single-nucleotide polymorphisms have been identified from genome-wide association studies, such as the two new loci in TSPAN15 (rs78707713) and SCL44A2 (rs2288904) genes. Risk factors are not always associated with VTE in isolation; however, and an understanding of how environmental and genetic factors interact may provide insight into the pathophysiology of VTE, possibly identifying opportunities for targeted prevention and treatment.
| S-EPMC5146955 | biostudies-literature
Project description:PurposeApproximately 10% of the general population has elevated blood concentrations of hepatic enzymes, which are linked to increased coagulation markers. We tested whether elevated hepatic enzymes are associated with increased risk of venous thromboembolism (VTE).MethodsWe followed 12,604 adults with measurements of alanine transaminase, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) prospectively for VTE occurrence.ResultsAST and GGT above the laboratory normal values were associated over two decades of follow-up with increased risk of total (n = 532) and provoked VTE (n = 332), but with not unprovoked VTE (n = 200). In a model adjusted for age, race, sex, hormone replacement, alcohol intake, diabetes, body mass index, estimated glomerular filtration rate, and C-reactive protein, the hazard ratios (HR) (95% confidence interval) for high versus normal AST were 1.46 (1.00-2.11) for total VTE and 1.83 (1.21-2.79) for provoked VTE. For high GGT, the HR were 1.34 (1.06-1.69) for total VTE and 1.43 (1.07-1.91) for provoked VTE. When follow-up was limited to the first 10 years, associations were even stronger (HR ≈ 1.7 for total VTE).ConclusionsElevated concentrations of two hepatic enzymes (AST and GGT) in this general middle-aged population are associated with a modestly increased risk of VTE.
| S-EPMC4254154 | biostudies-literature
Project description:The Roma populations in Central and Eastern Europe are two to three times more likely to have unmet health needs compared to non-Roma residents. The aim of the present study was to investigate the disparity in screening attendance between Hungarian-speaking Roma (R) and non-Roma (nR) women in Hungary (HU-R:322; nR:294), Romania (RO-R:258; nR:183), and Slovakia (SK-R:146; nR:163), while also identifying the factors that influence attendance at any kind of screening tests in both populations. In order to examine these factors, a multiple binary logistic regression was conducted. The findings revealed significant associations between attendance at any kind of screening tests and certain factors among different groups. Among Hungarian Roma women, it was found that having a chronic disease and smoking were linked to attendance at any kind of screening tests (p = 0.009). Specifically, having a chronic disease increased the odds of attendance (OR = 1.71 [1.01, 2.90]), while smoking decreased the odds (OR = 0.57[0.365, 0.91]). In Romania, the study found that not having health insurance decreased the odds of attendance among Roma women (OR = 0.50 [0.27, 0.91]), whereas having a chronic disease increased the odds (OR = 2.87 [1.44, 5.72]) (p = 0.006). Among non-Roma women in Romania, physical inactivity was associated with a decreased likelihood of attendance at any kind of screening tests (OR = 0.48 [0.25, 0.95]). Among Slovakian Roma women, not having health insurance (OR = 0.09[0.02, 0.36]) and smoking (OR = 0.25[0.11, 0.61]) were found to decrease the odds of attendance (p < 0.001). On the other hand, non-Roma women in Slovakia with chronic diseases were more likely to attend at any kind of screening tests (OR = 2.52[1.12, 5.66]). Our research emphasizes the impact of lacking health insurance on screening attendance, particularly among the Roma population. It also highlights the significance of health-related behaviours such as smoking and physical inactivity in relation to missed screening tests, which in turn contribute to the development of non-communicable diseases. Therefore, promoting targeted screening programs for the Roma community is crucial to ensure their access to screening tests, especially in cases of chronic illnesses.
| S-EPMC10771837 | biostudies-literature
Project description:A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.
| S-EPMC7153877 | biostudies-literature
Project description:AimCholesteryl ester transfer protein (CETP) is an important lipid transfer factor in plasma that enhances prothrombinase activity in purified systems. This study was conducted to test the association of plasma CETP activity with venous thrombosis (VTE) and to address the procoagulant mechanism of CETP activity in prothrombinase assays.MethodsWe measured CETP lipid transfer activity in plasmas of 49 male VTE patients and in plasmas of matched controls. CETP procoagulant activity was tested in purified prothrombinase systems.ResultsCETP lipid transfer activity levels were significantly higher in VTE patients than in controls (p=0.0008). A subset of patients carrying the CETP mutations Ala373Pro and Arg451Gln, which were also linked to the VTE risk, showed significantly higher plasma CETP activity than the noncarriers. The plasma CETP activity negatively correlated with APTT, suggesting that the CETP activity is associated with plasma coagulability. Recombinant (r) CETP bound to both factor Xa (Kd=15 nM) and Gla-domainless factor Xa (Kd=59 nM), whereas rCETP enhanced prothrombin activation by factor Xa, but not by Gla-domainless factor Xa. rCETP also required factor Va for enhancement of prothrombinase activity. When we addressed the effects of mutations in CETP on prothrombinase activity, Gln451-rCETP was found to have five-fold higher thrombin generation activity than wt-rCETP or Pro373-rCETP.ConclusionsElevated CETP lipid transfer activity in plasma was associated with the risk of VTE. Gln451-CETP, which is linked to VTE, has much higher procoagulant activity than wt-CETP. CETP might act as a physiologic procoagulant by mechanisms that involve its direct binding to factor Xa.
| S-EPMC5064881 | biostudies-literature
Project description:Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
| S-EPMC10247781 | biostudies-literature
Project description:ObjectiveVenous thromboembolism (VTE) is a life threating complication in intensive care units (ICUs). This study aimed to pool the prevalence of VTE and examined the risk factors of VTE in intensive care patients worldwide.MethodsA systematic search in PubMed, EMBASE and Web of Science databases was performed. Studies reported that the data on the prevalence of VTE or relevant information were synthesized using a random-effects model.ResultsA total of 42 studies reporting on 27,344 patients were included. The pooled prevalence of VTE was 10.0% (95% CI: 7.0-14.0%). Subgroup and metaregression analyses found that thromboprophylaxis strategy, simplified acute physiology score (SAPS II), age, study quality, sample size, malignancy, sex, spinal cord injury and injury severity score (ISS) moderated the prevalence of VTE in intensive care patients.ConclusionsThe present meta-analysis revealed a high prevalence of VTE in critically ill patients. The risk factors of VTE included thromboprophylaxis strategy, SAPS II, age, malignancy, sex, spinal cord injury and ISS. Therefore, we need to pay more attention to high-risk populations of VTE in intensive care patients.
| S-EPMC9698016 | biostudies-literature