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Genetics of coronary heart disease: towards causal mechanisms, novel drug targets and more personalized prevention.

Coronary heart disease (CHD) is an archetypical multifactorial disorder that is influenced by genetic susceptibility as well as both modifiable and nonmodifiable risk factors, and their interactions. Advances during recent years in the field of multifactorial genetics, in particular genomewide association studies (GWASs) and their meta-analyses, have provided the statistical power to identify and

A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease

Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucl

Hospital Admissions for Ischemic Stroke: Does Long-Term Exposure to Air Pollution Interact with Major Risk Factors?

Background: The aim was to investigate whether the effects of major risk factors for ischemic stroke were modified by long-term exposure to air pollution in Scania, southern Sweden. Methods: Cases were defined as first-ever ischemic strokes in patients born between 1923 and 1965 during 2001-2006 (n = 7,244). Data were collected from The Swedish National Stroke Register (Riks-stroke) and the Malmo

Factor H Autoantibodies in Patients with Antiphospholipid Syndrome and Thrombosis.

Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome, but can also be detected in patients with rheumatoid arthritis and in patients positive for lupus anticoagulants and thus potentially antiphospholipid syndrome (APS). To our knowledge, no data are available on the association between the presence of FH autoantibodies in APS and clinical manifestation

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and

Essentials of Nursing Care in Randomized Controlled Trials of Nurse-Led Interventions in Somatic Care: A Systematic Review

Background: Nursing practice has to contribute to evidence pointing out why there is a need for more nurse-designed randomized control trials (RCTs) focusing on evidence-based practice (EBP).How far this EBP has progressed in different health aspects is usually established by systematic reviews of RCTs. Nurse-led RCTs exist but no study has addressed the essentials of nursing care. Aim: The aim wa

Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro

Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells

Post-Genomic Update on a Classical Candidate Gene for Coronary Artery Disease: ESR1

Background-After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor alpha (ESR1) have shown conflicting results,

Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-c

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies compris

Dietary Flavonoid Intake and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort

We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer

The Effect of Nanoparticles on Amyloid Aggregation Depends on the Protein Stability and Intrinsic Aggregation Rate

Nanoparticles interfere with protein amyloid formation. Catalysis of the process may occur due to increased local protein concentration and nucleation on the nanoparticle surface, whereas tight binding or a large particle/protein surface area may lead to inhibition of protein aggregation. Here we show a clear correlation between the intrinsic protein stability and the nanoparticle effect on the ag

Limitations in the Use of Unipolar Charging for Electrical Mobility Sizing Instruments: A Study of the Fast Mobility Particle Sizer

A comparison between three different types of particle sizing instruments (fast mobility particle sizer, FMPS; electrical low pressure impactor, ELPI; and scanning mobility particle sizer, SMPS) and one condensation particle counter (CPC) was made to compare instrument response in terms of size distributions and number concentration. Spherical oil droplets in 39 different sizes, with geometric mea

Plasma level of the endogenous sodium pump ligand marinobufagenin is related to the salt-sensitivity in men.

Salt-induced elevation of the endogenous digitalis like sodium pump ligand marinobufagenin (MBG) in the Dahl salt-sensitive rats resulted in elevated blood pressure (BP). Here, we tested, in humans, whether MBG levels are related to ambulatory 24-h BP (ABP), controlled long-term increase of salt-intake induces changes in MBG and any salt-induced change in MBG is related to salt sensitivity.

Loci influencing blood pressure identified using a cardiovascular gene-centric array

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestr

Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII.

Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cance

Syndromes of orthostatic intolerance: a hidden danger.

Orthostatic hypotension (OH) is a relatively common heterogenous and multifactorial disorder, traditionally classified as neurogenic (less common but often more severe), or non-neurogenic (more common, with no direct signs of autonomic nervous system disease). The different clinical variants of orthostatic intolerance include initial, classical and delayed OH as well as postural tachycardia syndro

Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-ana