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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults
Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to in
A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.
BackgroundObesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity.MethodsIn the PROMIS study, a cross-sectional study based in Pakistan, we calculated BMI varia
The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis
Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have
Reduced morbidity at diagnosis and improved glycemic control in children previously enrolled in DiPiS follow-up
Aims/hypothesis: Children participating in longitudinal type 1 diabetes prediction studies were reported to have less severe disease at diabetes diagnosis. Our aim was to investigate children who from birth participated in the Diabetes Prediction in Skane (DiPiS) study for metabolic status at diagnosis and then continued to be followed for 2 yr of regular clinical care. Methods: Children, followed
The Dark Side of the Swoon: antihypertensive treatment in the elderly.
We would like to thank Prof. Dal Moro for his valuable contribution[1]. Indeed, many patients, especially those who are older and who suffer from several concomitant diseases, are at risk of being "overtreated with good intentions". The main problem is that the diagnosis of essential hypertension is at times assigned very liberally based on a single ambulatory measurement without taking into consi
TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene varian
Effects of Weight Loss, Weight Cycling, and Weight Loss Maintenance on Diabetes Incidence and Change in Cardiometabolic Traits in the Diabetes Prevention Program.
This study examined specific measures of weight loss in relation to incident diabetes and improvement in cardiometabolic risk factors.RESEARCH DESIGN AND METHODS: This prospective, observational study analyzed nine weight measures, characterizing baseline weight, short- versus long-term weight loss, short- versus long-term weight regain, and weight cycling, within the Diabetes Prevention Program (
Abdominal and gynoid adiposity and the risk of stroke
Background: Previous studies have indicated that fat distribution is important in the development of cardiovascular disease (CVD). We investigated the association between fat distribution, as measured by dual energy X-ray absorptiometry (DXA), and the incidence of stroke. Methods: A cohort of 2751 men and women aged >= 40 years was recruited. Baseline levels of abdominal, gynoid and total body fat
Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats
Aims/hypothesis High plasma copeptin, a marker of vasopressin (VP) secretion, has been shown to be associated with the metabolic syndrome and development of type 2 diabetes in humans. The present study was designed to determine the long-term influence of plasma VP concentration in a rodent model prone to metabolic dysfunction. Methods Obese Zucker rats and their lean counterparts were submitted fo
Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study
Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) coh
Reflex syncope, anxiety level, and family history of cardiovascular disease in young women: case-control study.
Anxiety is an emotion, which stimulates sympathetic nervous outflow potentially facilitating vasovagal reflex syncope (VVS) but reports on anxiety levels in patients with VVS are sparse.
Blood Pressure Loci Identified with a Gene-Centric Array
Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combin
Expression Quantitative Trait Loci Acting Across Multiple Tissues Are Enriched in Inherited Risk for Coronary Artery Disease.
-Despite recent discoveries of new genetic risk factors, the majority of risk for coronary artery disease (CAD) remains elusive. As the most proximal sensor of DNA variation, RNA abundance can help identify subpopulations of genetic variants active in and across tissues mediating CAD risk through gene expression.
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
Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.
The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.
Vasopressin induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4 T MRI.
From histopathological specimens, endolymphatic hydrops has been demonstrated in association with inner ear disorders. Recent studies have observed findings suggestive of hydrops using MRI in humans. Previous studies suggest that vasopressin may play a critical role in endolymph homeostasis and may be involved in the development of Ménière's disease. In this study we evaluate the effect of vasopre
A population-based study on the prevalence of NASH using scores validated against liver histology.
Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes
We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genom
Common Polymorphisms in the CYP11B1 and CYP11B2 Genes: Evidence for a Digenic Influence on Hypertension
The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conv
