Genetic Association Between ICAM-1 Gene Variants and Susceptibility to Ischemic Cardiomyopathy.

ABSTRACT: The current work was aimed at exploring the association between single nucleotide polymorphisms (SNPs) in the ICAM-1 gene, along with the identification of additional haplotypes and their potential role in the susceptibility to ischemic cardiomyopathy (ICM). The control group underwent a Hardy-Weinberg equilibrium test. The associations of genotypes and alleles with susceptibility to ICM were then analyzed using logistic regression analysis. Subsequently odds ratios (ORs) along with 95% confidence intervals (95% CI) were calculated. Interaction analysis was conducted between these SNPs. Furthermore, linkage disequilibrium analysis and haplotype analysis were performed on SNPs that showed interactions with each other. The incidence of ICM was significantly higher among individuals carrying the T allele of rs3093032 (OR = 2.032, 95% CI, 1.275-3.241, P = 0.003) relative to those with the C allele. In addition, CT genotype carriers had a higher susceptibility to ICM than CC genotype carriers (OR = 2.490, 95% CI, 1.445-4.29, P = 0.001). Furthermore, 3 SNPs (rs3093032, rs923366, rs3093030) exhibited a strong interaction with each other, whereas rs281437 showed no interaction with the other 3 SNPs. Individuals carrying the C rs3093032 -T rs923366 -C rs3093030 haplotype had an elevated risk of ICM compared with those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.280, 95% CI, 1.568-3.315, P < 0.001). Moreover, individuals carrying the T rs3093032 -C rs923366 -C rs3093030 haplotype were more susceptible to ICM than those carrying the C rs3093032 -C rs923366 -C rs3093030 haplotype (OR = 2.388, 95% CI, 1.469-3.880, P < 0.001). Regarding rs3093032, the minor alleles and haplotypes are associated with an increased ICM risk: 3 SNPs (rs3093032, rs923366, rs3093030) in ICAM-1 have strong interaction with each other.

Development and Validation of a Novel Nomogram to Predict the Impact of the Polymorphisms of the Variants of ICAM-1 Gene on the Prognosis of Ischemic Cardiomyopathy.

Object: This study investigated the correlation between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic model for predicting the prognosis ICM on the basis of ICAM-1 gene variants. Methods: The current study included totally 576 patients with ICM. All patients are randomly divided into training group with 399 patients and validation group with 177 patients. The prognostic model was constructed by using the data of training group. Univariable Cox-regression analysis was performed, including clinical and gene variants, then used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. Furthermore, multivariate Cox-regression was applied to build the prognostic nomogram model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model. Results: Predicting factors rs281430, ventricular arrhythmia, treating by PCI or CABG, use of ß-blockers, heart rate (HR), serum sodium level, left ventricular end-diastolic diameter (LVDD) were the risk factors of the prognosis of ICM, incorporated these factors into the prognostic nomogram model. The constructed nomogram performed well in discrimination ability, as observed by the ROC and C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. Conclusion: rs281430 mutation (from AA genotype to AG or GG genotype) is a risk factor for ICM patients to have a higher survival probability; the survival probability of ICM patients with the mutant genotype (AG or GG) is lower than those with the wild genotype (AA).

Development and validation of a novel nomogram to predict the impact of the polymorphism of the ICAM-1 gene on the prognosis of ischemic cardiomyopathy.

The current study investigated the association between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic nomogram for ICM on the basis of ICAM-1 gene variants. The current study included totally 252 patients with ICM. In addition, PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used to genotype SNPs in the ICAM-1 gene in the patients. Later, the nomogram model was built by combining clinical data and ICAM-1 gene variants. This study used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection into an ICM prognostic model. Furthermore, multivariate Cox-regression was applied to build the prognostic model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model, and the bootstrap method was adopted for internal validation. predicting factors rs112872667, treating by PCI or CABG, ventricular arrhythmia, left ventricular end-diastolic diameter (LVDD), use of ß-blockers, systolic blood pressure (SBP), heart rate (HR), and serum sodium were incorporated into the prognostic nomogram. The constructed nomogram performed well in discrimination ability, as observed by the time-dependent C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. mutation of rs112872667 have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC). Mutation of rs112872667 in ICAM-1 gene have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC).

Study on the Mechanism of NLRP3/IL-1/ NF-κB Signaling Pathway and Macrophage Polarization in the Occurrence and Development of VTE.

BACKGROUND: The role of inflammation in venous thromboembolism (VTE) has been the focus of recent research. The NLRP3/IL-1/NF-κB signaling pathway and cytokines such as IL-1, regulated by macrophage polarization, may be the key indicators of a prethrombotic state; however, the mechanisms by which they affect the occurrence of VTE remain unclear. METHODS: We used neurobiological clamps to stimulate the vein wall to induce vascular endothelial damage to generate a rat model of VTE, applied enzyme-linked immunosorbent assay and real time-polymerase chain reaction technology to identify key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65), gene mRNA levels and protein expression levels of the NLRP3/IL-1/NF-κB signaling pathway in each group of Sprague Dawley rats, and observed the polarization state of M1 (CD86) and M2 (CD206) macrophages using immunohistochemistry. RESULTS: A dark red, small thrombus developed in the inferior vena cava immediately after modeling in the model and inhibitor groups. The plasma levels of IL-1 and TNF-α, mRNA expression of key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65), and expression of key proteins (IL1ß, Caspase-1, NLRP3, and NF-κB P65) in VTE model rats were significantly higher than inhibitor, sham operation, and normal control groups (P < 0.05). Six hours after VTE modeling, M1 type macrophages were more significantly increased than M2 type macrophages in thrombus tissue (P < 0.05). CONCLUSIONS: Our analyses demonstrated that the nod-like receptor protein3/Interleukin-1/nuclear factor-κB signaling pathway and macrophage polarization are important in the occurrence and development of VTE and that their target regulation may become a new strategy for VTE prevention and treatment.

Development and validation of a predictive model of the impact of single nucleotide polymorphisms in the ICAM-1 gene on the risk of ischemic cardiomyopathy.

Objective: Previous research has linked single nucleotide polymorphisms (SNPs) in the ICAM-1 gene to an increased risk of developing ischemic cardiomyopathy (ICM); however, a diagnostic model of ICM according to the ICAM-1 variant has not yet been developed. Therefore, this study aimed to explore the correlation between SNPs in ICAM-1 and the presence of ICM, along with developing a diagnostic model for ICM based on the variants of the ICAM-1 gene. Method: This study recruited a total of 252 patients with ICM and 280 healthy controls. In addition, all the participants were genotyped for SNPs in the ICAM-1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using the training dataset of 371 people, we constructed a nomogram model based on ICAM-1 gene variants and clinical variables. To optimize the feature choice for the ICM risk model, a least absolute shrinkage and selection operator (LASSO) regression model was adopted. We also employed multivariable logistic regression analysis to build a prediction model by integrating the clinical characteristics chosen in the LASSO regression model. Following the receiver operating characteristic (ROC), a calibration plot and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical usefulness of the predictive model. Result: The predictors involved in the prediction nomogram included age, smoking, diabetes, low-density lipoprotein-cholesterol, hemoglobin, N-terminal pro-B-type natriuretic peptide, ejection fraction, and the rs5491 SNP. The nomogram model exhibited good discrimination ability, with the AUC value of ROC of 0.978 (95%CI: 0.967-0.989, P < 0.001) in the training group and 0.983 (95% CI: 0.969-0.998, P < 0.001) in the validation group. The Hosmer-Lemeshow test demonstrated good model calibration with consistency (P training group = 0.937; P validation group = 0.910). The DCA showed that the ICM nomogram was clinically beneficial, with the threshold probabilities ranging from 0.0 to 1.0. Conclusion: The AT genotype in rs5491 of the ICAM-1 gene was associated with having a higher frequency of ICM. Individuals carrying the mutant AT genotype showed a 5.816-fold higher frequency of ICM compared with those with the AA genotype. ICM patients with the AT genotype also had a higher rate of cardiogenic death. We, therefore, developed a nomogram model that could offer an individualized prediction of ICM risk factors.

Idiopathic Venous Thromboembolism and Metabolic Syndrome: A Meta-analysis.

Metabolic syndrome (MetS) is a recognised risk factor for arterial thromboembolism. However, whether MetS is also a risk factor for venous thromboembolism (VTE) is uncertain. PubMed, Embase, Web of science, and Cochrane databases were searched for case-control and cohort studies as well as conference proceedings of the International society on Thrombosis and Haemostasis (ISTH), and the Women's Health International Symposium Thrombosis and Hemostasis Branch (WHITH) published on or before March 1, 2021, to identify eligible studies. All included articles were assessed by two investigators using the Newcastle-Ottawa scale (NOS). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between VTE and MetS by using random or fixed-effects models. There were 31 case-control and 5 cohort studies with a total of 78,529 participants that fulfilled the inclusion criteria, MetS (OR 1.49; 95% CI 1.29-1.73) and its critical component obesity (OR 2.03; 95% CI 1.74-2.37), hypertension (OR 1.40; 95% CI 1.19-1.64) and diabetes mellitus (OR 1.22; 95% CI 1.01-1.48) were significant risk factors for VTE. MetS and its critical component obesity may contribute to the multifactorial pathogenesis of VTE. Key Words: Venous thromboembolism, Metabolic syndrome, Obesity.

Correlation Study of the Long-Term Prognosis of Venous Thromboembolism and Inflammatory Gene Polymorphisms.

BACKGROUND: Venous thromboembolism (VTE) is the third most common cause of cardiovascular death worldwide, following coronary heart disease and stroke, and many risk factors for VTE are not yet clear. Our study investigated the association between multiple inflammatory gene polymorphisms and VTE prognosis, aiming to find a new predictor of VTE prognosis. METHODS: Based on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE. All subjects were followed up for 5 years. RESULTS: The 5-year follow-up results of this study showed that 62 of the 284 patients (21.83%) had reached the endpoint (all-cause death). Kaplan-Meier survival analyses revealed that the mortality rate of VTE patients with a high Simplified Pulmonary Embolism Severity Index (SPESI) score and carrying IL-1 rs1800587 mutation genotypes was significantly increased (log-rank p=0.000 and 0.034 respectively). The multifactor Cox regression results confirmed that the mortality rate of patients who carrying IL-1 rs1800587 mutation genotypes was significantly increased (HR=2.982; 95% CI: 1.681-5.100). The mortality rate of those carrying IL-1 rs1143634 mutation genotypes was significantly decreased (HR=0.294; 95% CI: 0.132-0.652). There were no significant differences in mortality rates between wild-type and mutant genotypes of IL-1 rs1143634, IL-1 rs2234650, SAA rs11603089, and TNF-α rs1800629 (P>0.05). CONCLUSION: A high SPESI score and the presence of the IL-1 rs1800587 mutant genotype predict shorter survival in patients with VTE, whereas the IL-1 rs1143634 genotype is associated with a lower mortality rate. Screening for mutations in inflammation-related genes has prognostic value in the clinical management of VTE.

Correlation study of venous thromboembolism with SAA, IL-1, and TNF-a levels and gene polymorphisms in Chinese population.

BACKGROUND: The relationship between inflammation and venous thromboembolism (VTE) has not been fully elucidated. METHODS: Based on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1), and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE and 268 healthy controls. RESULTS: Levels of SAA (P=0.032), IL-1 (P=0.045), and TNF-a (P=0.040) were significantly higher in the VTE group than in the control group. Recessive model analysis of the IL-1 rs1800587 variant showed that the risk of VTE in patients with the GG + GA genotype was significantly higher than that in patients with the AA genotype [odds ratio (OR): 4.444; 95% CI: 1.466-13.470]. Recessive model analysis of the IL-1 rs2234650 polymorphism showed that the risk of VTE in patients with the CC + CT genotype was significantly lower than that in patients with the TT genotype (OR: 0.500; 95% CI: 0.268-0.934). Multivariate logistic regression analysis showed that the TT genotype at IL-1 rs2234650 (OR: 2.086; 95% CI: 1.091-3.985) was an independent risk factor for VTE. The AA genotype of IL-1 rs1800587 (OR: 0.226; 95% CI: 0.074-0.890) was an independent protective factor against VTE. CONCLUSIONS: In summary, an intrinsic relationship may exist between inflammatory activation and the occurrence of VTE.