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The Correlation Between FGB Promoter Polymorphism and Clotting Function in Patients With Idiopathic Lower Extremity Deep Venous Thrombosis.

ABSTRACT: To explore the possible single nucleotide polymorphisms (SNPs) sites in the promoter region of fibrinogen B β (FGB), and construct logistic regression model and haplotype model, so as to reveal the influence of FGB promoter SNPs on susceptibility, hemodynamics and coagulation function of lower extremity deep venous thrombosis (LEDVT) in the genetic background. LEDVT patients (120) and healthy people (120) were taken as case and control objects, respectively. SNPs and their genotypes of FGB promoter were detected by promoter sequencing and PCR-RFLP. The parameters of coagulation system were evaluated. There were 6 SNPs in FGB promoter, which were β-148C/T, β-249C/T, β-455G/A, β-854G/A, β-993C/T and β-1420G/A. The genotype and allele frequency of β-1420 G/A, β-455G/A, β-249c/T and β-148C/T were significantly different between the LEDVT group and the control group, but not β-993C/T and β-854G/A. In addition, we found that the higher the content of Fibrinogen (FG), the higher the risk of LEDVT. The risk of LEDVT increased by 4.579 times for every unit increase of fibrinogen. We also found that FG, PT and APTT in LEDVT group were higher than those in control group, while TT was lower than those in control group; Furthermore, there was no significant difference in all coagulation indexes among 6 SNP genotypes in LEDVT group, while a significant difference was found between the 2 genotypes of β-993C/T in the control group. β-993C/T may indirectly affect the susceptibility of LEDVT by improving the basic level of plasma FG.

SUBMITTER: Han S

PROVIDER: S-EPMC8485564 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveAlthough previous studies have shown that gut microbiota may be involved in the occurrence of deep venous thrombosis (DVT), the specific link between the two remains unclear. The present study aimed to explore this question from a genetic perspective.Materials and methodsGenome-wide association study (GWAS) summary data of DVT were obtained from the UK Biobank (N = 9,059). GWAS summary data of the gut microbiota were obtained from the Flemish Gut Flora Project (N = 2,223) and two German cohorts (FoCus, N = 950; PopGen, N = 717). All the participants were of European ancestry. Linkage disequilibrium score (LDSC) regression has great potential for analyzing the heritability of disease or character traits. LDSC regression was used to analyze the genetic correlation between DVT and the gut microbiota based on the GWAS summary data obtained from previous studies. Mendelian randomization (MR) was used to analyze the genetic causal relationship between DVT and the gut microbiota. We used the random effects inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode to perform MR analysis. We performed a sensitivity analysis of the MR analysis results by examining heterogeneity and horizontal pleiotropy.ResultsLinkage disequilibrium score analysis showed that Streptococcaceae (correlation coefficient = -0.542, SE = 0.237, P = 0.022), Dialister (correlation coefficient = -0.623, SE = 0.316, P = 0.049), Streptococcus (correlation coefficient = -0.576, SE = 0.264, P = 0.029), and Lactobacillales (correlation coefficient = -0.484, SE = 0.237, P = 0.042) had suggestive genetic correlation with DVT. In addition, the MR analysis showed that Streptococcaceae had a positive genetic causal relationship with DVT (P = 0.027, OR = 1.005). There was no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05).ConclusionIn this study, four gut microbes (Streptococcaceae, Dialister Streptococcus, Lactobacillales) had suggestive genetic correlations with DVT, and Streptococcaceae had a positive causal relationship with DVT. Our findings provide a new research direction for the further study of and prevention of DVT.

Project description:BackgroundThe systemic immune-inflammation index (SII), as a novel inflammatory biomarker, has recently attracted attention in cardiovascular disease research. However, the relationship between SII and risk of lower extremity deep venous thrombosis (LEDVT) remains unclear to date. Thus, this study aimed to explore the association in a large sample over a 10-year period (2012-2022).MethodsAll hospitalized patients undergoing lower extremity compression ultrasonography (CUS) examination were consecutively screened by searching our hospital information system database. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value for high and low SII group. Multivariate logistic regression analyses were performed to investigate the relationship between SII and LEDVT risk. Propensity score matching (PSM), subgroup and sensitivity analyses were also conducted. Moreover, restricted cubic spline (RCS) regression and two-piecewise linear regression models were used to assess the dose-response relationship between natural log transformed SII [ln(SII)] and risk of LEDVT.ResultsA total of 16,725 consecutive hospitalized patients were included, and 1,962 LEDVT events occurred. After adjusting for confounding factors, patients in the high SII group (≥ 574.2 × 109/L) showed a 1.740-fold risk of LEDVT (95% CI: 1.546-1.959, P < 0.001), and elevated ln(SII) was associated with a 36.1% increased risk of LEDVT (95% CI: 1.278-1.449, P < 0.001). PSM, subgroup and sensitivity analyses confirmed the robustness of the association. A non-linear relationship was observed (P non-linear < 0.001), with a threshold value of 5.6 × 109/L for all LEDVT events. Above the threshold, each unit increase in ln(SII) had a 1.369-fold higher risk of LEDVT (95% CI: 1.271-1.475, P < 0.001). The association also existed in both distal and proximal LEDVT.ConclusionElevated SII is significantly associated with an increased risk of LEDVT in hospitalized patients. Additionally, the association is non-linear and exhibit a threshold effect.

Project description:ImportanceVenous thromboembolism is the second overall leading cause of death for patients with cancer, and there is an approximately 2-fold increase in fatal pulmonary embolism (PE) in patients with cancer. Inferior vena cava (IVC) filters are designed to prevent PE, but defining the appropriate use of IVC filters in patients with cancer remains a substantial unmet clinical need.ObjectiveTo evaluate the association of IVC filters with the development of PE in patients with cancer and deep venous thrombosis (DVT).Design, setting, and participantsA population-based cohort study was conducted using administrative data on 88 585 patients from the state inpatient databases for California (2005-2011) and Florida (2005-2014). Based on diagnostic and procedure codes, patients with cancer and acute lower extremity DVT were identified. All subsequent hospital visits for these patients were evaluated for the placement of an IVC filter, the development of new PE, the development of new DVT, and in-hospital mortality. Data analysis was performed from September 1 to December 1, 2019.ExposuresPlacement of an IVC filter.Main outcomes and measuresThe association of IVC filter placement with rates of new PE and DVT was estimated using a propensity score matching algorithm and competing risk analysis.ResultsThe study cohort comprised 88 585 patients (45 074 male; median age, 71.0 years [range, 1.0-104.0 years]) with malignant neoplasms who presented to a health care institution with a diagnosis of acute lower extremity DVT. Of these patients, 33 740 (38.1%) underwent IVC filter placement; patients with risk factors such as upper gastrointestinal bleeding (odds ratio, 1.32; 95% CI, 1.29-1.37), intracranial hemorrhage (odds ratio, 1.21; 95% CI, 1.19-1.24), and coagulopathy (odds ratio, 1.09; 95% CI, 1.08-1.10) were more likely to receive an IVC filter. A total of 4492 patients (5.1%) developed a new PE after their initial DVT diagnosis. There was a significant improvement in PE-free survival for these patients compared with those who did not receive IVC filters across the full, unbalanced study cohort as well as after propensity score matching and competing risk analysis (hazard ratio, 0.69; 95% CI, 0.64-0.75; P < .001). Furthermore, IVC filter placement reduced the development of PE in patients with very high-risk malignant neoplasms (eg, pancreaticobiliary cancer), high-risk malignant neoplasms (eg, lung cancer), and low-risk malignant neoplasms (eg, prostate cancer). After accounting for anticoagulation use and imbalanced risk factors, IVC filter placement did not increase the risk of new DVT development.Conclusions and relevanceThis study suggests that, for patients with cancer and DVT and bleeding risk factors, IVC filter placement is associated with an increased rate of PE-free survival.

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The Correlation Between FGB Promoter Polymorphism and Clotting Function in Patients With Idiopathic Lower Extremity Deep Venous Thrombosis.

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