Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Nocturnal gastro-oesophageal reflux (nGOR) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGOR is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population-based study. We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a 9-year interval. They participated in structured interviews, answered questionnaires, and underwent spirometries and methacholine challenge testing. nGOR was defined by reported symptoms. Subjects with persistent nGOR (n=123) had an independent increased risk of new asthma at follow-up (OR 2.3, 95% CI 1.1-4.9). Persistent nGOR was independently related to onset of respiratory symptoms (OR 3.0, 95% CI 1.6-5.6). The risk of developing symptoms of OSA was increased in subjects with new and persistent nGOR (OR 2.2, 95% CI 1.3-1.6, and OR 2.0, 95% CI 1.0-3.7, respectively). No significant association was found between nGOR and lung function or bronchial responsiveness. Persistent symptoms of nGOR contribute to the development of asthma and respiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGOR. These findings provide evidence that nGOR may play a role in the genesis of respiratory symptoms and diseases.Swedish Heart and Lung foundation Swedish Asthma and Allergy Association Vardal Foundation for Health Care Science and Allergy Research Icelandic Research Council Landspitali University Hospital Fund Research Foundation of Flanders, Belgiu

Suspected association of ventricular arrhythmia with air pollution in a motorbike rider: a case report

<p>Abstract</p> <p>Introduction</p> <p>Premature ventricular complexes are to some extent a normal finding in healthy individuals and the prevalence increases with age and is more common in men. Premature ventricular complexes can occur in association with a variety of stimuli, and a lesser known cause is the association between air pollution and ventricular arrhythmias.</p> <p>Case presentation</p> <p>A previously healthy man started to ride a lightweight motorbike in heavy traffic. A few weeks later he was admitted to hospital with premature ventricular complexes in bigeminy, which decreased after a few days when he was not exposed to exhaust fumes. A few weeks later he started using the motorbike again and the same symptoms developed once more, only to subside when he stopped riding in heavy traffic.</p> <p>Conclusion</p> <p>Studies have shown an association between air pollution and premature ventricular complexes and other kinds of arrhythmias. The mechanism may be changes in cardiac autonomic function, including heart rate and heart rate variability. Air pollution should be considered when patients present with arrhythmias and no other causes are found.</p

Genetical genomics: spotlight on QTL hotspots

No abstract available

Statistical independence of the colocalized association signals for type 1 diabetes and RPS26 gene expression on chromosome 12q13

Following the recent success of genome-wide association studies in uncovering disease-associated genetic variants, the next challenge is to understand how these variants affect downstream pathways. The most proximal trait to a disease-associated variant, most commonly a single nucleotide polymorphism (SNP), is differential gene expression due to the cis effect of SNP alleles on transcription, translation, and/or splicing gene expression quantitative trait loci (eQTL). Several genome-wide SNP–gene expression association studies have already provided convincing evidence of widespread association of eQTLs. As a consequence, some eQTL associations are found in the same genomic region as a disease variant, either as a coincidence or a causal relationship. Cis-regulation of RPS26 gene expression and a type 1 diabetes (T1D) susceptibility locus have been colocalized to the 12q13 genomic region. A recent study has also suggested RPS26 as the most likely susceptibility gene for T1D in this genomic region. However, it is still not clear whether this colocalization is the result of chance alone or if RPS26 expression is directly correlated with T1D susceptibility, and therefore, potentially causal. Here, we derive and apply a statistical test of this hypothesis. We conclude that RPS26 expression is unlikely to be the molecular trait responsible for T1D susceptibility at this locus, at least not in a direct, linear connection

Expression quantitative trait loci are highly sensitive to cellular differentiation state

Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different ce

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands