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Asthma genetics

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https://www.readbyqxmd.com/read/28102054/extracellular-vesicles-a-key-mediator-to-link-environmental-microbiota-to-airway-immunity
#1
REVIEW
Youngwoo Choi, Hanki Park, Hae Sim Park, Yoon Keun Kim
Asthma is considered the hallmark of chronic airway inflammation, in which several inflammatory cells of the innate and adaptive immune system act together. The disease is thought to be caused by a combination of genetic and environmental factors; however, precise mechanisms for airway inflammation remain unclear. The human microbiota provides an increasingly favored explanation for inflammatory diseases; an altered microbiota composition has been shown to regulate immune responses. However, given the complexity of the microbiota, additional research is needed to elucidate its role in the development of disease...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28100615/rhinovirus-c-asthma-and-cell-surface-expression-of-virus-receptor-cdhr3
#2
Ann C Palmenberg
Human rhinoviruses of the A, B, and C species are defined agents of the common cold. But more than that, the RV-A and RV-C are the dominant cause of hospitalization-category infections in young children, especially those with asthma. The RV-C use of cadherin-related family member 3 (CDHR3) as its cellular receptor, creates a direct phenotypic link between human genetics ("G" vs "A" alleles cause Cys529 vs Tyr529 protein variants) and the efficiency with which RV-C can infect cells. With a lower cell surface display density, the human-specific Cys529 variant apparently confers partial protection from the severest virus-induced asthma episodes...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100614/human-rhinovirus-diversity-and-evolution-how-strange-the-change-from-major-to-minor
#3
Nicole Lewis-Rogers, Jon Seger, Frederick R Adler
: Rhinoviruses are the most common cause of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell-surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino-acid substitution at exposed sites in the capsid proteins VP2, VP3 and VP1 tend to be elevated in minor-group relative to major-group viruses, while rates at buried sites show no consistent differences...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28093362/hypoxia-inducible-factor-1%C3%AE-inhibition-modulates-airway-hyperresponsiveness-and-nitric-oxide-levels-in-a-balb-c-mouse-model-of-asthma
#4
Carola Dewitz, Elisa McEachern, Stephanie Shin, Kathryn Akong, Dale G Nagle, David H Broide, Praveen Akuthota, Laura E Crotty Alexander
: Hypoxia inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-1α antagonist YC-1 suppressed the increase in HIF-1α expression seen in control AIAD mice...
January 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28079285/a-pathway-based-association-study-reveals-variants-from-wnt-signaling-genes-contributing-to-asthma-susceptibility
#5
A Barreto-Luis, A Corrales, M Acosta-Herrera, C Gonzalez-Colino, J Cumplido, J Martinez-Tadeo, A Carracedo, J Villar, T Carrillo, M Pino-Yanes, C Flores
BACKGROUND: Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. OBJECTIVE: To reveal novel asthma susceptibility genes by means of a pathway-based association study. METHODS: Based on summary data from a previous a genome-wide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis...
January 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28078100/asthma-costs-and-social-impact
#6
REVIEW
Carlos Nunes, Ana Margarida Pereira, Mário Morais-Almeida
In recent decades, both asthma prevalence and incidence have been increasing worldwide, not only due to the genetic background, but mainly because of the effect of a wide number of environmental and lifestyle risk factors. In many countries noncommunicable diseases, like asthma, are not yet considered a healthcare priority. This review will analyze and discuss disparities in asthma management in several countries and regions, such as access to healthcare human resources and medications, due to limited financial capacity to develop strategies to control and prevent this chronic disease...
2017: Asthma research and practice
https://www.readbyqxmd.com/read/28076799/adenylyl-cyclase-type-9-gene-polymorphisms-are-associated-with-asthma-and-allergy-in-brazilian-children
#7
Helena M P Teixeira, Neuza M Alcantara-Neves, Maurício Barreto, Camila A Figueiredo, Ryan S Costa
Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders...
January 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28070732/the-clinical-and-laboratory-spectrum-of-dedicator-of-cytokinesis-8-immunodeficiency-syndrome-in-patients-with-a-unique-mutation
#8
Arnon Broides, Amarilla B Mandola, Jacov Levy, Baruch Yerushalmi, Vered Pinsk, Michal Eldan, George Shubinsky, Nurit Hadad, Rachel Levy, Amit Nahum, Miriam Ben-Harosh, Atar Lev, Amos Simon, Raz Somech
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis...
January 10, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28069425/an-epigenome-wide-association-study-of-total-serum-immunoglobulin-e-in-hispanic-children
#9
Wei Chen, Ting Wang, Maria Pino-Yanes, Erick Forno, Liming Liang, Qi Yan, Donglei Hu, Daniel E Weeks, Andrea Baccarelli, Edna Acosta-Perez, Celeste Eng, Yueh-Ying Han, Nadia Boutaoui, Catherine Laprise, Gwyneth A Davies, Julian M Hopkin, Miriam F Moffatt, William O C M Cookson, Glorisa Canino, Esteban G Burchard, Juan C Celedón
BACKGROUND: Total immunoglobulin E (IgE) is a therapeutic target in allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE in an epigenome-wide association study (EWAS) of Caucasians. Whether DNA methylation of eosinophils explains those findings is insufficiently understood. METHODS: We tested for association between genome-wide DNA methylation in WBCs and total IgE in two studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL, n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II, n = 573)...
January 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28068894/strain-differences-in-a-murine-model-of-air-pollutant-induced-nonatopic-asthma-and-rhinitis
#10
Jack R Harkema, Lucas A Hotchkiss, Nicholas A Vetter, Daven N Jackson-Humbles, Ryan P Lewandowski, James G Wagner
Ozone is an irritating gas found in photochemical smog. Epidemiological associations have been made between the onset of asthma and childhood exposures to increasing levels of ambient ozone (i.e., air pollutant-induced nonatopic asthma). Individuals, however, vary in their susceptibility to this outdoor air pollutant, which may be due, in part, to their genetic makeup. The present study was designed to test the hypothesis that there are murine strain-dependent differences in pulmonary and nasal pathologic responses to repeated ozone exposures...
January 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28068891/immunological-variation-due-to-genetics-of-inflammatory-snps-and-age-and-impact-on-disease-manifestation
#11
Gary R Burleson
The immune system is a critical component in defense against viral, bacterial, parasitic, and fungal diseases. Immunological mechanisms, including immunological mediators, innate immunity, cell-mediated immunity, and humoral-mediated immunity, serve to maintain homeostasis and protect the host from disease. Immunological variation can impact defense mechanisms, however. Two factors in particular that can influence immune function are the single nucleotide polymorphisms (SNPs) and aging. SNPs affecting inflammatory cytokines are an important modifier involved in a number of diseases such as asthma, periodontal disease, atherosclerosis, diabetic retinopathy, psoriasis, and osteoporosis...
January 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28057889/association-between-il-13-1923c-t-polymorphism-and-asthma-risk-a-meta-analysis-based-on-26-case-control-studies
#12
Yueli Xu, Junjuan Li, Zhaolei Ding, Juan Li, Bin Li, Zhengang Yu, Wei Tan
Asthma is a serious and hereditary respiratory disorder affecting all age groups. Interleukin (IL)-13 is a central regulator of allergic inflammation. The purpose of this study was to estimate the relationship between IL-13 +1923C/T polymorphism and asthma susceptibility. Relevant case-control studies published between January 2000 and July 2016 were searched in the online databases. Review Manage (RevMan) 5.3 was used to conduct the statistical analysis. The pooled odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of association...
January 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28052796/genetic-variants-of-the-gasdermin-b-gene-associated-with-the-development-of-aspirin-exacerbated-respiratory-diseases
#13
Lyoung Hyo Kim, HunSoo Chang, Suhg Namgoong, Ji On Kim, Hyun Sub Cheong, Seo-Gyeong Lee, Jong Sook Park, Ae Rin Baek, So-My Koo, Inseon S Choi, Mi-Kyeong Kim, Hea-Sim Park, Choon-Sik Park, Hyoung Doo Shin
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by a severe and sudden asthma attack after aspirin ingestion in patients with asthma. We studied associations with six common single nucleotide polymorphisms (SNP) of the gasdermin B gene (GSDMB). OBJECTIVE: DNA obtained from 572 patients with asthma (with AERD, n = 165; and with aspirin-tolerant asthma, n = 407) and 391 normal controls was subjected to genotyping of six SNPs of GSDMB. METHODS: An association analysis between GSDMB variants and AERD, with a fall rate of the forced expiratory volume in the first second of expiration (FEV1), was performed by using logistic and regression models...
January 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28052339/overview-of-systematic-reviews-in-allergy-epidemiology
#14
REVIEW
Jon Genuneit, Annina M Seibold, Christian J Apfelbacher, George N Konstantinou, Jennifer J Koplin, Stefania La Grutta, Kirsty Logan, Michael R Perkin, Carsten Flohr
BACKGROUND: There is a substantial body of evidence on the epidemiology of allergic conditions, which has advanced the understanding of these conditions. We aimed to systematically identify systematic reviews and meta-analyses on the epidemiology of allergic diseases to assess what has been studied comprehensively and what areas might benefit from further research. METHODS: We searched PubMed and EMBASE up to 12/2014 for systematic reviews on epidemiological research on allergic diseases...
January 4, 2017: Allergy
https://www.readbyqxmd.com/read/28036144/revisiting-type-2-high-and-type-2-low-airway-inflammation-in-asthma-current-knowledge-and-therapeutic-implications
#15
Douglas Robinson, Marc Humbert, Roland Buhl, Alvaro A Cruz, Hiromasa Inoue, Stephan Korom, Nicola A Hanania, Parameswaran Nair
Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. Type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems...
December 30, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28030377/microbes-allergic-sensitization-and-the-natural-history-of-asthma
#16
Halie M Anderson, Daniel J Jackson
PURPOSE OF REVIEW: Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention. RECENT FINDINGS: This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections...
December 24, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28030376/the-effect-of-obesity-weight-gain-and-weight-loss-on-asthma-inception-and-control
#17
Erick Forno, Juan C Celedón
PURPOSE OF REVIEW: There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'. RECENT FINDINGS: Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis, systemic inflammation, production of adipokines, impaired glucose-insulin metabolism, altered nutrient levels, genetic and epigenetic changes, and alterations in the airway and/or gut microbiome...
December 24, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28030368/sphingolipids-ormdl3-and-asthma-what-is-the-evidence
#18
Tilla S Worgall
PURPOSE OF REVIEW: Genome-wide association studies identified ORMDL3, a protein of the endoplasmic reticulum, as a significant asthma risk factor. ORMDL3 is one of three ORMDL proteins that integrate multiple signals to maintain sphingolipid homeostasis. Studies that investigated potential mechanisms for how increased ORMDL3 might affect asthma are summarized. RECENT FINDINGS: Investigations focused on decreased sphingolipid synthesis and on the unfolded protein response because ORMDL3 had been implicated in both...
December 24, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28005431/lung-development-and-aging
#19
Andrew Bush
The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung function. Despite reports from numerous big cohorts, no single adult life factor, including smoking, accounts for this accelerated decline. By contrast, five childhood risk factors (maternal and paternal asthma, maternal smoking, childhood asthma and respiratory infections) are strongly associated with an accelerated rate of lung function decline and COPD...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27996019/intragenic-cftr-duplication-and-5t-12tg-variant-in-a-patient-with-non-classic-cystic-fibrosis
#20
Patricia B S Celestino-Soper, Edward Simpson, Danika Tumbleson Brink, Ty C Lynnes, Stephen Dlouhy, Matteo Vatta, Jana Yeley, Cynthia Brown, Shaochun Bai
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene. Individuals with other variants may present with classic, non-classic, or milder forms of CF due to lower levels of functional CFTR protein...
December 20, 2016: Scientific Reports
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