Genetic analysis of plasma von Willebrand factor antigen levels as a risk factor for arterial and venous thrombosis

We carried out the first genome-wide linkage analysis in British families for VWF levels.  ABO and VWF loci were specifically examined.  The results showed that VWF levels are highly heritable 42% (P>0.000001) with age and C-reactive protein (CRP) the main covariates.  The ABO locus was strongly associated with VWF levels (P=2x10-18), but linkage was modest (LOD = 1.6).  VWF gene marker showed no significant association or linkage with phenotype.  Genome-wide linkage analysis, conditioned on age and ABO genotypes, revealed regions with potential linkage.  Highlighted regions were on chromosomes 2 and 3 (LOD = 1.78 & 1.08 respectively) and two areas on chromosome 12 (LOD = 1.5 & 1.3).  Inflammatory biomarkers concentrations were also investigated.  Heritabilities of CRP and tumour necrosis factor-alpha (TNF-a) were significantly high 38% and 47% respectively, while interleukin-6 was not heritable.  VWF levels showed significant genetic correlation with CRP. As ABO group has a major role in determining VWF levels, if the VWF stroke association is causal, blood groups should be associated with stroke (Mendelian Randomisation).  ABO genotype frequencies in stroke patients were investigated by a case-control study (503 objectively diagnosed cases and 327 controls).  Non-O groups were not significantly over-represented in stroke cases (OR 1.1, CI95 0.83-1.47).  Monte Carlo method, taking into account ABO effect on VWF levels, showed no association between ABO genotypes and stroke risk.  This was reinforced by the findings of the systematic review we conducted on ABO groups and stroke.  In contrast to results obtained from venous TE systematic review, where almost a two fold increased risk was found with non-O groups vs. O group.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Interleukin-4 polymorphism in Egyptian patients with type-2 diabetic nephropathy

Abstract: The effects of environmental and genetic factors on the development of diabetic complications are well-documented. The roles of inflammatory processes on the development of these complications including diabetic nephropathy were established. Cytokines have great roles in the development of diabetic nephropathy. Polymorphism in the 590-region of interleukin-4 gene is associated with the regulation of expression of this gene. During these investigations, peripheral blood was collected from 100 patients with type-2 diabetes mellitus with nephropathy and 100 diabetics without nephropathy (control). DNA was extracted and a polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique was performed to examine polymorphisms in the -590 region of the IL-4 gene. Obtained results revealed that the frequency of allele T was higher among patients with diabetic nephropathy than among the control. In addition, most of patients with allele T had overt albuminurea, higher blood pressure, renal dysfunction and dyslipidemia than patients with allele C. In conclusion, these findings suggest that patients with allele T are more liable to develop diabetic nephropathy with most of the micro-and macro-vascular complications

Effect of environmental pollutants particulate matter PM2.5, PM10, nitrogen dioxide (NO2) and ozone (O3) on obesity

Background: Environmental pollution is a highly challenging global health concern, affecting the natural ecosystem and human health. The obesity risk is allied to diverse factors, including genetics, behaviour, food, and socio-cultural conditions, however, literature is lacking in exploring the effect of environmental pollution on obesity and the causal pathways are not fully understood. Therefore, this study aimed to investigate the effect of environmental pollutants particulate matter PM2.5 μm, PM10 μm, Nitrogen Dioxide (NO2), and ground level Ozone (O3) on obesity. Methods: This study recorded data on air pollutants and obesity using the electronic platforms Pub Med, Web of Science, Scopus, and Google Scholar. The keywords included for the literature search were based on a combination of two main aspects, which were used to represent exposure (air pollutants), and outcome (obesity). Initially, 324 articles and reports were identified, and after revising the abstracts and full articles, 12 studies were selected for a detailed analysis and discussion. The Odds Ratio (OR) and 95 % confidence intervals (CIs) were extracted to investigate the impact between air pollutants and obesity. The Cochrane chi-squared test (Chi2), fixed-effects design was used when I2  0.05; otherwise, a random-effects model was adopted. Results: Environmental pollutants, particulate matter PM2.5 (OR = 1.18; 95 % CI: 1.10–1.25p < 0.01), PM10 (OR = 1.11; 95 % CI: 1.02–1.20; p < 0.01), Nitrogen Dioxide NO2 (OR = 1.14; 95 % CI: 1.02–1.28; p = 0.03), ground-level Ozone O3 (OR = 1.01; 95 % CI: 1.00–1.01; p = 0.01) were significantly and positively associated with obesity. Conclusions: Environmental pollution could be a risk factor for obesity. The potential mechanisms involved in the pathogenesis of this relationship are oxidative stress, inflammation, hormonal disruption, and adipose tissue function alteration. Addressing this multifaceted issue requires collaboration between public health officials, policymakers, and the public at large. Moreover, raising public awareness is a crucial step towards mitigating the impact of environmental pollution on obesity

Neutrophil chemokines levels in different stages of nephrotic syndrome

Nephrotic syndrome (NS) is a disease of glomerular filtration barrier failure presenting with variable degrees of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Inflammation may contribute to the pathogenesis of NS. The aim of this study was to monitor the serum levels of three cytokines [i.e., granulocyte chemotactic protein-2 (GCP-2), growth-related oncogene-α (GRO-α), and interleukin-8 (IL-8)] in different stages of NS and to find out whether changes in the levels of these cytokines could be related to the severity of NS. This study included 125 patients who were divided into 40 patients with nephrotic range proteinuria (NRP), 45 patients with NS, and 40 patients who were in remission. This study also included 80 healthy participants as a control group. Enzyme-linked immunosorbent assay was used for the determination of the plasma levels of GRO-α, GCP-2, and IL-8. GCP-2 plasma levels were significantly higher in the NS and NRP groups when compared to the control group, whereas the GRO-α and IL-8 levels were significantly higher in all patient groups in comparison with the control group. All these chemokine levels were significantly decreased in remission as compared with the participants in the NS group (P <0.0001). There was a significant correlation between the cytokine levels and proteinuria and serum albumin in the NS group (P <0.0001). However, in the follow-up group, GCP-2 levels were significantly lower during remission as compared to those with active NS (P <0.0001). Our findings suggest that the pro-inflammatory cytokines GCP-2, GRO-α, and IL-8 could play a role in the pathogenesis of NS, particularly glomerular permeability

α-Adducin gene promoter DNA methylation and the risk of essential hypertension

This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = −0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders

Thrombin generation and endothelial dysfunctional markers in different stages of nephrotic syndrome

Objectives: Venous thromboembolism is an important and potentially life-threatening complication of nephrotic syndrome (NS). This study aims to evaluate the functional test of thrombin generation (TG) in different stages of NS; determine its relation with the coagulation screening tests (prothrombin time [PT] and activated partial thromboplastin time), hemostatic activation markers (thrombin–antithrombin complex [TAT] and prothrombin fragment 1+2 [PF1+2]), and von Willebrand factor (vWF) and its proteolytic enzyme ADAMTS-13; and determine the correlation between TG and NS severity, as reflected by the levels of proteinuria and albumin. Materials and Methods: This case–control cross-sectional study included 125 patients (n = 40, nephrotic range proteinuria; n = 45, NS; n = 40, remission) and 80 controls. Calibrated automated thrombogram assay (endogenous thrombin potential [ETP]) was performed to determine TG. TAT, PF1+2, vWF, and ADAMTS-13 were measured using enzyme-linked immunosorbent assay. Results: TG (ETP), TAT, PF1+2, and vWF levels were significantly higher in all of the patient groups (P < 0.0001) than in the control group. ADAMTS-13 levels were significantly lower in the NS group (P < 0.0001) than in the control group. Conclusion: Our findings confirm activation of the coagulation pathway in nephrotic patients. However, the degree of hypercoagulopathy (especially TG [ETP]) is positively correlated with proteinuria. Proteinuria could be considered an indirect indicator of the highest risk of thrombotic disease in patients with NS

Compliance with and awareness about long-term oral anticoagulant therapy among Saudi patients in a University Hospital, Riyadh, Saudi Arabia

Context: Oral anticoagulant therapy (OAT) is one of the most widely used therapies. Being on such regimens requires high degree of compliance and adequate knowledge to avoid serious complications. Aims: This study aims to assess compliance with and awareness about OAT among Saudi patients, and their willingness to use the point-of-care (POC) international normalized ratio (INR) testing devices for self-monitoring. Settings and Design: This cross-sectional study was conducted at a tertiary hospital in Riyadh, Saudi Arabia, over 6 months. Subjects and Methods: A face-to-face interview has been carried out for all patients based on the questionnaire carried out for all patients based on the questionnaire. Results were analyzed according to demographics, adherence, knowledge, and INR control. Statistical Analysis Used: Statistical Package for the Social Sciences version 19 software (SPSS Inc., Chicago, IL, USA) was used. Results: One hundred sixty-two patients were interviewed, of which females (69.1%) exceeded males (30.1%). Most of them were on warfarin (80.2%), received education by their physicians. In general, patients had poor knowledge and medium adherence (53.1%) (scored < 50%). About 24% of the poor knowledge group (PKG) were highly adherent compared to 14.5% of the fine knowledge group (FKG). However, 53.2% of FKG had a controlled INR where this percentage reduces to 27% in PKG. The most incorrect answered question in both groups was related to warfarin-drug-interactions (75.3%). The majority (74.7%) was eager to make use of the POC-INR devices. Conclusions: The participants' knowledge was generally poor but level of knowledge did not play a role in compliance. Regardless, an education program should be accommodated to help patients in improving their medication control and reducing clinical visits. The majority was willing to adopt (POC) INR devices that will certainly help them in managing their treatment and potentially reducing adverse clinical outcomes

Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects