Atrial natriuretic peptide and three-dimensional echocardiography after transcatheter closure of atrial septal defect

<p>Abstract</p> <p>Background</p> <p>Atrial septal defect (ASD) accounts for 10% of all congenital heart lesions and represent the third most congenital cardiac defect seen in adults. Atrial natriuretic peptide (ANP) is an important regulator of the sodium and volume homeostasis. This study was designed to investigate the changes in plasma ANP concentrations and three-dimensional echocardiography (3DE) measurements of cardiac volume in patients with ASD during transcatheter closure of defect.</p> <p>Methods</p> <p>Plasma ANP concentrations and transthoracic 3DE measurements of right ventricular volume were performed in 46 patients with ASD before closure, and at 3 days after closure. 22 healthy subjects matched for age, sex served as control subjects.</p> <p>Results</p> <p>The 46 patients (20 men, 26 women; mean age 26.32 ± 13.28, range 6 to 63 years) were diagnosed to secundum ASD (the stretched diameters of ASD were from 9~36(25.34 ± 7.80 mm), and had been successfully placed Amplatzer septal occluder (the sizes of occluder were from 11 to 40 mm). The results showed that compared with control subjects, plasma ANP concentrations were elevated in patients with ASD. Plasma ANP concentrations positively correlated significantly with pulmonary artery pressure (PAP) (r = 0.74, <it>p </it>< 0.05) and 3DE measurements of cardiac volumes (right ventricular end-diastolic (r = 0.50, <it>p </it>< 0.05) and end-systolic volume (r = 0.50, <it>p </it>< 0.05) and negatively correlated with RVEF (r = -0.38, <it>p </it>< 0.05). Transthoracic 3DE measurements of right ventricular volume and plasma ANP concentrations decreased significantly at 3 days after closure (<it>p </it>< 0.05) compared with it before closure.</p> <p>Conclusion</p> <p>Plasma ANP concentrations were markedly elevated in patients with pulmonary arterial hypertension and right ventricular volume overload and decreased significantly after closure of ASD. This study suggested that ANP may help to identify patients with ASD complicated by pulmonary arterial hypertension and right ventricular volume overload that demanded early intervention and may become effective marker for evaluating changes in cardiac load after transcatheter ASD closure.</p

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases