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Asthma genetics

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https://www.readbyqxmd.com/read/27933519/heterogeneous-stock-populations-for-analysis-of-complex-traits
#1
Leah C Solberg Woods, Richard Mott
Heterogeneous Stock (HS) populations allow for fine-resolution genetic mapping of a variety of complex traits. HS mice and rats were created from breeding together eight inbred strains, followed by maintaining the colony in a manner that minimizes inbreeding. After 50 or more generations of breeding, the resulting animals' chromosomes represent a genetic mosaic of the founders' haplotypes, with the average distance between recombination events in the centiMorgan range. This allows for genetic mapping to only a few Mb, a much smaller region than what can be identified using traditional F2 intercross or backcross mapping strategies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27929694/dna-methylation-levels-associate-with-race-and-childhood-asthma-severity
#2
Marcia A Chan, Christina E Ciaccio, Nicole M Gigliotti, Mo Rezaiekhaligh, Jacob A Siedlik, Kevin Kennedy, Charles S Barnes
OBJECTIVE: Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression...
December 8, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27927014/genetic-modification-of-the-lung-directed-toward-treatment-of-human-disease
#3
Dolan Sondhi, Katie Stiles, Bishnu P De, Ronald G Crystal
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy and lung cancer, infections such as respiratory syncytial virus and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection and lung injury...
December 7, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27920557/effect-of-smoking-on-the-genetic-makeup-of-toll-like-receptors-2-and-6
#4
Muhammad Kohailan, Mohammad Alanazi, Mahmoud Rouabhia, Abdullah Alamri, Narasimha Reddy Parine, Abdullah Alhadheq, Santhosh Basavarajappa, Abdul Aziz Abdullah Al-Kheraif, Abdelhabib Semlali
BACKGROUND: Cigarette smoking is a major risk factor for lung cancer, asthma, and oral cancer, and is central to the altered innate immune responsiveness to infection. Many hypotheses have provided evidence that cigarette smoking induces more genetic changes in genes involved in the development of many cigarette-related diseases. This alteration may be from single-nucleotide polymorphisms (SNPs) in innate immunity genes, especially the toll-like receptors (TLRs). OBJECTIVE: In this study, the genotype frequencies of TLR2 and TLR6 in smoking and nonsmoking population were examined...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27901618/genome-wide-interaction-analysis-of-air-pollution-exposure-and-childhood-asthma-with-functional-follow-up
#5
Anna Gref, Simon Kebede Merid, Olena Gruzieva, Stéphane Ballereau, Allan Becker, Tom Bellander, Anna Bergström, Yohan Bossé, Matteo Bottai, Moira Chan-Yeung, Elaine Fuertes, Despo Ierodiakonou, Ruiwei Jiang, Stéphane Joly, Meaghan Jones, Michael S Kobor, Michal Korek, Anita L Kozyrskyj, Ashish Kumar, Nathanaël Lemonnier, Elaina MacIntyre, Camille Ménard, David Nickle, Ma'en Obeidat, Johann Pellet, Marie Standl, Annika Sääf, Cilla Söderhäll, Carla Mt Tiesler, Maarten van den Berge, Judith M Vonk, Hita Vora, Cheng-Jian Xu, Josep M Antó, Charles Auffray, Michael Brauer, Jean Bousquet, Bert Brunekreef, W James Gauderman, Joachim Heinrich, Juha Kere, Gerard H Koppelman, Dirkje Postma, Christopher Carlsten, Göran Pershagen, Erik Melén
RATIONALE: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent, and may depend on genetic factors. OBJECTIVES: 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. METHODS: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctor's diagnosis of asthma up to 8 years in three European birth cohorts (n=1,534) with look-up for interaction in two separate North American cohorts, CHS and CAPPS/SAGE (n=1,602 and 186 subjects, respectively)...
November 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27899370/benign-reactive-lymphoid-hyperplasia-of-the-conjunctiva-in-childhood
#6
Adel G AlAkeely, Hind M Alkatan, Adel H Alsuhaibani, Hisham AlKhalidi, Leen Abu Safieh, Sarah E Coupland, Deepak P Edward
BACKGROUND/AIM: Our aim is to the report the clinical and histopathological features of benign reactive lymphoid hyperplasia (BRLH) of the conjunctiva in children and the outcomes of treatment. METHODS: A retrospective chart review was performed for children aged 0-18 years, diagnosed with conjunctival BRLH from January 2000 to December 2013 at two large ophthalmology hospitals in the Middle East. Data were collected on patient demographics, features of the lesions, the site of the lesion, location, adnexal involvement, lymph nodes involvement, local spread, histopathology and molecular genetic studies of the cases (if available), outcomes of treatment and recurrence...
November 29, 2016: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/27895690/rhinovirus-and-childhood-asthma-an-update
#7
REVIEW
Dae Jin Song
Asthma is recognized as a complex disease resulting from interactions between multiple genetic and environmental factors. Accumulating evidence suggests that respiratory viral infections in early life constitute a major environmental risk factor for the development of childhood asthma. Respiratory viral infections have also been recognized as the most common cause of asthma exacerbation. The advent of molecular diagnostics to detect respiratory viruses has provided new insights into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/27885204/genetic-interactions-between-adrb2-and-ptger4-on-responses-to-salmeterol-or-montelukast-in-japanese-patients-with-mild-persistent-asthma
#8
Hideyasu Yamada, Hironori Masuko, Toshihide Inui, Jun Kanazawa, Yohei Yatagai, Tohru Sakamoto, Hiroaki Iijima, Satoshi Konno, Kaoruko Shimizu, Hironi Makita, Masaharu Nishimura, Fumio Kokubu, Takefumi Saito, Takeo Endo, Hiroki Ninomiya, Norihiro Kaneko, Nobuyuki Hizawa
BACKGROUND: Long-acting β2-agonists (LABA) and leukotriene receptor antagonists (LTRA) are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. In our previous study, the Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene did not influence the differential bronchodilator effect of salmeterol versus montelukast as an add-on therapy to ICS within 16 weeks of follow-up (the J-Blossom study)...
2016: Arerugī, [Allergy]
https://www.readbyqxmd.com/read/27878470/%C3%AE-2-agonists
#9
Charlotte K Billington, Raymond B Penn, Ian P Hall
History suggests β agonists, the cognate ligand of the β2 adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations...
November 23, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27871876/disaggregating-asthma-big-investigation-vs-big-data
#10
Danielle Belgrave, John Henderson, Angela Simpson, Iain Buchan, Christopher Bishop, Adnan Custovic
We are facing a major challenge in bridging the gap between identifying subtypes of asthma, to understanding causal mechanisms, and translating this knowledge into personalized prevention and management strategies. In recent years, "big data" has been sold as a panacea for generating hypotheses and driving new frontiers of healthcare; the idea that the data must and will speak for themselves is fast becoming a new dogma. One of the dangers of ready accessibility of healthcare data and computational tools for data analysis is that the process of data mining may become uncoupled from the scientific process of clinical interpretation, understanding the provenance of the data and external validation...
November 18, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27865862/impaired-mucus-clearance-exacerbates-allergen-induced-type-2-airway-inflammation-in-juvenile-mice
#11
Benedikt Fritzsching, Matthias Hagner, Lu Dai, Sandra Christochowitz, Raman Agrawal, Charlotte van Bodegom, Simone Schmidt, Jolanthe Schatterny, Stephanie Hirtz, Ryan Brown, Michelle Goritzka, Julia Duerr, Zhe Zhou-Suckow, Marcus A Mall
BACKGROUND: Type 2 airway inflammation plays a central role in the pathogenesis of allergen-induced asthma, but the underlying mechanisms remain poorly understood. We recently demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile Scnn1b-transgenic (Scnn1b-Tg) mice. OBJECTIVE: To determine the role of impaired mucus clearance in the pathogenesis of allergen-induced type 2 airway inflammation and identify cellular sources of the signature cytokine IL-13...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27865540/cofactors-and-comorbidities-in-patients-with-aspirin-nsaid-hypersensitivity
#12
REVIEW
M Sánchez-Borges, F Caballero-Fonseca, A Capriles-Hulett
Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals...
November 16, 2016: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/27863396/p2rx4-deficiency-in-mice-alleviates-allergen-induced-airway-inflammation
#13
Andreas Zech, Benjamin Wiesler, Cemil Korcan Ayata, Tilmann Schlaich, Thorsten Dürk, Madelon Hoßfeld, Nicolas Ehrat, Sanja Cicko, Marco Idzko
Compelling evidences point out a crucial role for extracellular nucleotides such as adenosine triphosphate (ATP) during inflammatory conditions. Once released into the extracellular space, ATP modulates migration, maturation and function of various inflammatory cells via activating of purinergic receptors of the P2Y- and P2X- family. P2RX4 is an ATP-guided ion channel expressed on structural cells such as alveolar epithelial and smooth muscle cells as well as inflammatory cells including macrophages, dendritic cells (DCs) and T cells...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848966/17q21-asthma-risk-variants-switch-ctcf-binding-and-regulate-il-2-production-by-t-cells
#14
Benjamin Joachim Schmiedel, Grégory Seumois, Daniela Samaniego-Castruita, Justin Cayford, Veronique Schulten, Lukas Chavez, Ferhat Ay, Alessandro Sette, Bjoern Peters, Pandurangan Vijayanand
Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter the expression of ORMDL3; however, the molecular mechanisms by which these variants perturb gene expression and the cell types in which this effect is most prominent are unclear. We found several 17q21 variants overlapped enhancers present mainly in primary immune cell types. CD4(+) T cells showed the greatest increase (threefold) in ORMDL3 expression in individuals carrying the asthma-risk alleles, where ORMDL3 negatively regulated interleukin-2 production...
November 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27842596/integrative-analysis-of-genetic-data-sets-reveals-a-shared-innate-immune-component-in-autism-spectrum-disorder-and-its-co-morbidities
#15
Sumaiya Nazeen, Nathan P Palmer, Bonnie Berger, Isaac S Kohane
BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that tends to co-occur with other diseases, including asthma, inflammatory bowel disease, infections, cerebral palsy, dilated cardiomyopathy, muscular dystrophy, and schizophrenia. However, the molecular basis of this co-occurrence, and whether it is due to a shared component that influences both pathophysiology and environmental triggering of illness, has not been elucidated. To address this, we deploy a three-tiered transcriptomic meta-analysis that functions at the gene, pathway, and disease levels across ASD and its co-morbidities...
November 14, 2016: Genome Biology
https://www.readbyqxmd.com/read/27836433/sex-differences-in-the-epidemiology-clinical-features-and-pathophysiology-of-migraine
#16
REVIEW
Kjersti Grøtta Vetvik, E Anne MacGregor
Migraine is two to three times more prevalent in women than men, and women report a longer attack duration, increased risk of headache recurrence, greater disability, and a longer period of time required to recover. Conditions recognised to be comorbid with migraine include asthma, anxiety, depression, and other chronic pain conditions, and these comorbidities add to the amount of disability in both sexes. Migraine-specifically migraine with aura-has been identified as a risk factor for vascular disorders, particularly in women, but because of the scarcity of data, the comparative risk in men has yet to be established...
November 8, 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27836009/how-can-we-optimise-inhaled-beta2-agonist-dose-as-reliever-medicine-for-wheezy-pre-school-children-study-protocol-for-a-randomised-controlled-trial
#17
Somnath Mukhopadhyay, Paul Seddon, Gemma Earl, Emma Wileman, Liz Symes, Cathy Olden, Corinne Alberti, Stephen Bremner, Alison Lansley, Colin N A Palmer, Nicole Beydon
BACKGROUND: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 μg) may be ineffective or likely to induce unnecessary side effects...
November 11, 2016: Trials
https://www.readbyqxmd.com/read/27835674/lymphocyte-activation-dynamics-is-shaped-by-hereditary-components-at-chromosome-region-17q12-q21
#18
Amado Carreras-Sureda, Fanny Rubio-Moscardo, Alex Olvera, Jordi Argilaguet, Kerstin Kiefer, Beatriz Mothe, Andreas Meyerhans, Christian Brander, Rubén Vicente
Single nucleotide polymorphisms (SNPs) located in the chromosome region 17q12-q21 are risk factors for asthma. Particularly, there are cis-regulatory haplotypes within this region that regulate differentially the expression levels of ORMDL3, GSDMB and ZPBP2 genes. Remarkably, ORMDL3 has been shown to modulate lymphocyte activation parameters in a heterologous expression system. In this context, it has been shown that Th2 and Th17 cytokine production is affected by SNPs in this region. Therefore, we aim to assess the impact of hereditary components within region 17q12-q21 on the activation profile of human T lymphocytes, focusing on the haplotype formed by allelic variants of SNPs rs7216389 and rs12936231...
2016: PloS One
https://www.readbyqxmd.com/read/27830580/effect-of-prenatal-antioxidant-intake-on-infants-respiratory-infection-is-modified-by-a-cd14-polymorphism
#19
Seo Ah Hong, Eun Lee, Sung Ok Kwon, Kyung Won Kim, Youn Ho Shin, Kang Mo Ahn, Eun-Jin Kim, Jeom-Gyu Lee, Se-Young Oh, Soo-Jong Hong
BACKGROUND: Prenatal maternal diet may influence disease susceptibility in offspring with specific genetic backgrounds. We hypothesized that interactions between prenatal antioxidant intake and polymorphisms in immunity genes infl uence respiratory tract infection (RTI) susceptibility in infants at 12 months of age. METHODS: This study included 550 infants. In the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort study, prenatal maternal diet was assessed by administering a food frequency questionnaire...
November 3, 2016: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/27826966/association-of-mbl-with-work-related-respiratory-symptoms-in-bakery-workers
#20
Mi Ae Kim, Moon Kyung Yoon, Seung Hyun Kim, Hae Sim Park
Baker's asthma is the most prevalent occupational asthma, and IgE-mediated response is known as a major pathogenesis. However, recent studies have suggested the involvement of innate immune response because wheat flour contains bacterial endotoxins or lipopolysaccharides. To further understand a role of innate immune response in the development of work-related respiratory symptoms (WRS) in bakery workers, we investigated mannose-binding lectin (MBL), one of the initiating components of the complement cascade in a single cohort of bakery workers...
January 2017: Allergy, Asthma & Immunology Research
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