👤 K E Berge

COPD is characterised by chronic airflow limitation and persistent inflammation. Inhaled corticosteroids (ICS) are often used to reduce airway inflammation in patients. However, the response to ICS treatment varies among patients, and blood eosinophils may not fully reflect treatment effectiveness. In this study, we aim to identify gene modules associated with ICS responsiveness and assess the underlying biological pathways. We included 55 patients from the GLUCOLD study with mild-moderate COPD treated with ICS for 6 months with available gene expression data from biopsies. Treatment response was defined as changes in post-bronchodilator forced expiratory volume in 1 s (FEV We identified four gene modules associated to ICS-induced improvement in FEV This study identified gene modules and pathways associated with ICS responsiveness in COPD, providing a potential mechanistic explanation for the variability in ICS treatment responsiveness in COPD. Show less

The GramAdapt Social Contact Dataset is a curated dataset of 34 language pairs with qualitative and quantifiable data on social interaction and aspects of societal multilingualism. The language pairs were sampled globally to represent the world's linguistic diversity. The dataset can be used to interrogate the social dimensions of language contact independently or in conjunction with appropriate linguistic data. The data were collected by distributing a questionnaire to experts who have experience with either one or both of the language communities of a pair. The data represent subjective expert assessments based on choices from predetermined answers which can be quantified. Authors 1, 2 and 3 manually checked the response to identify possible misjudgments or misunderstandings. This results in a dataset containing 13,493 data points. This dataset is a first of its kind in the field of linguistics, built upon wide findings from sociolinguistics, historical linguistics, psycholinguistics, and linguistic anthropology. Show less

The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors. To identify gene-environment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels. We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO In the European cohorts, 186 SNPs had an interaction P < 1 × 10 Our results indicated that gene-environment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2. Show less

Type 1 hyperlipoproteinemia is an autosomal recessive disorder characterized by severely elevated plasma triglyceride levels, which may lead to abdominal pain and pancreatitis, eruptive xanthomas and failure to thrive. Mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), lipase maturing factor 1 (LMF1) or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) have been found to cause Type 1 hyperlipoproteinemia. Two sibpairs belonging to two different branches of an extended pedigree were referred for molecular elucidation for their increased plasma triglyceride levels, which untreated were >27 mmol/L. The genes LPL, APOC2, APOA5, LMF1 and GPIHBP1 were analyzed by DNA sequencing. No mutations were found in LPL, APOC2, APOA5 or LMF1. No PCR products were obtained for exons 3 and 4 of GPIHBP1 from DNA of the 4 affected subjects. Subsequent long-range PCR revealed that the four affected were homozygous for a deletion comprising exons 3 and 4 of GPIHBP1. No increase in LPL activity was found in post-heparin plasma from the subjects. Homozygosity for a deletion of exons 3 and 4 of GPIHBP1 results in Type 1 hyperlipoproteinemia. Show less

Genetic testing for hypertrophic cardiomyopathy (HCM) became available in Norway in 2003. Here, we describe the results of this testing in probands with HCM referred until the end of 2012. The translated exons of MYBPC3, MYH7, TNNI3, TNNT2, MYL2 and MYL3 were analyzed in two groups of probands. In Group 1, comprising 696 probands above 1 year of age, a mutation was found in 203 patients (29.2%). Of those, 5.9% were carriers of two mutations. Mean age in double mutation carriers, single mutation carriers and mutation negative probands was 44 years (± 19 years), 50 years (± 5 years) and 55 years (± 6 years), respectively. In Group 2, comprising 26 infants below the age of 1, a mutation was found in 15.4%. A total of 120 different mutations were found of which 51 (42.5%) were novel. Show less

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart. Show less

Several antipsychotic drugs (APDs) have high propensity to induce weight gain and dyslipidemia in patients, with clozapine and olanzapine as the most potent drugs. These lipid-related effects have been attributed to drug-mediated blockade or antagonism of histamine H1 and serotonin 5-HT2 receptors as well as activation of hypothalamic AMP-activated protein kinase. We recently showed that APDs activate lipid biosynthesis in cultured liver cells through stimulation of the sterol regulatory element-binding protein (SREBP) transcription factors. The objective of the study was to search for clozapine-related lipogenic effects in peripheral tissues in vivo using rat liver as target organ. Adult female Sprague-Dawley rats were administered single intraperitoneal injections of clozapine (25 and 50 mg/kg). Hepatic lipid levels were measured during a 48-h time course. Real-time quantitative PCR was used to analyze expression of genes involved in lipid biosynthesis, oxidation, efflux, and lipolysis. We identified an initial up-regulation of central lipogenic SREBP target genes, followed by a marked and sustained down-regulation. We also observed a sequential transcriptional response for fatty acid beta-oxidation and cholesterol efflux genes, normally controlled by the peroxisome proliferator activated receptor alpha and liver X receptor alpha transcription factors, and also down-regulation of genes encoding major lipases. The transcriptional responses were associated with a significant accumulation of triacylglycerol, phospholipids, and cholesterol in the liver. These results demonstrate that acute clozapine exposure affects SREBP-regulated lipid biosynthesis as well as other lipid homeostasis pathways. We suggest that such drug-induced effects on lipid metabolism in peripheral tissues are relevant for the metabolic adverse effects associated with clozapine and possibly other APDs. Show less

Hypertrophic cardiomyopathy is an autosomal dominant inherited disease characterized by ventricular hypertrophy and myofibril disarray. Mutations responsible for hypertrophic cardiomyopathy have been identified in 11 genes that encode for cardiac sarcomere proteins. Traditionally, hypertrophic cardiomyopathy due to mutation of the myosin-binding protein C gene (MYBPC3) has been thought to follow a benign course. We report a family with several members affected by hypertrophic cardiomyopathy in which there was a high incidence of sudden death. Disease was presumably caused by the substitution of cytosine by guanine at nucleotide 269 of MYBPC3 mRNA. This mutation, which has not previously been described, modifies codon 79, which encodes for the incorporation of a tyrosine, and gives rise to a stop codon. The mutation described here appears to confer a higher risk than that previously associated with hypertrophic cardiomyopathy due to MYBPC3 gene mutation. Show less