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

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

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

Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity