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Asthma genetics

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https://www.readbyqxmd.com/read/29451705/modeling-asthma-pitfalls-promises-and-the-road-ahead
#1
REVIEW
Helene F Rosenberg, Kirk M Druey
Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines...
February 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29444897/role-of-nkp46-natural-killer-cells-in-house-dust-mite-driven-asthma
#2
Eline Haspeslagh, Mary J van Helden, Kim Deswarte, Sofie De Prijck, Justine van Moorleghem, Louis Boon, Hamida Hammad, Eric Vivier, Bart N Lambrecht
House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69 + NK cells in the bronchoalveolar lumen...
February 14, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29427980/epidemiology-of-asthma-and-influence-of-ethnicity
#3
Theo J Moraes, Malcolm R Sears, Padmaja Subbarao
Asthma is a heterogeneous disorder with a complex etiology. Prevalence rates for asthma have been increasing in many countries over the past few decades. While it is unclear why this increase is occurring, the variation reported in asthma prevalence and severity associated with ethnicity offers some insight into the determinants of asthma. In this chapter, we discuss the data linking asthma to ethnicity and some of the factors that may explain this association. These include socioeconomic status, environmental exposures, the host microbiome, and genetics...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29427967/pleiotropic-effects-of-hypoglycemic-agents-implications-in-asthma-and-copd
#4
REVIEW
Paola Rogliani, Josuel Ora, Nicola Di Daniele, Davide Lauro
Diabetes mellitus (DM) is a complex multifactorial disease due to the interaction between environmental noxae and genetic predisposition. Furthermore, an increased association between DM, especially Type 2 diabetes mellitus (T2DM), and the onset of pulmonary function impairment with a bronchial hyperresponsiveness has been documented. DM is a risk factor for accelerated decline in FEV1 and the development of asthma and COPD. The increased blood glucose concentrations along with higher levels of oxidative stress and inflammation can influence the pulmonary function and, since hypoglycemic drugs can act on these different defects we can hypothesize their direct effect on obstructive pulmonary diseases...
February 7, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29416713/associations-of-tap1-genetic-polymorphisms-with-atopic-diseases-asthma-rhinitis-and-dermatitis
#5
Rongzeng Liu, Xiafei Chen, Jingjiao Qi
Controversial findings have been reported regarding to the effect of the transporter associated with antigen processing 1 (TAP1) polymorphisms exerted on the atopic diseases susceptibility. To gain a better understanding of the effects of TAP1 polymorphisms on the risk of atopic diseases, a retrospective study was carried out to evaluate the association of the most common TAP1 polymorphisms, rs1057141 and rs1135216, with the risk of atopic diseases. From studies published in PubMed, Embase, and Web of Science up to July 2017, ten eligible studies were selected for meta-analysis...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412180/as-you-eat-it-effects-of-prenatal-nutrition-on-asthma
#6
Kathleen Lee-Sarwar, Augusto A Litonjua
Asthma most frequently develops early in life, and increased recognition of the role of lifestyle and environmental factors in asthma susceptibility raises the possibility that dietary exposures during pregnancy may influence risk of asthma in offspring. This review discusses the latest evidence with regard to the effect of diet during pregnancy on childhood asthma risk, including potential mechanisms, outcomes of randomized clinical trials, and results from observational studies. Vitamin D and polyunsaturated fatty acid intake during pregnancy are highlighted as areas with large and growing bodies of literature to support a potential role in prenatal modulation of subsequent asthma risk...
February 2, 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29411558/interactions-between-bisphenol-a-exposure-and-gstp1-polymorphisms-in-childhood-asthma
#7
Tien Jen Lin, Wilfried J J Karmaus, Mei Lien Chen, Jiin Chyr Hsu, I Jen Wang
PURPOSE: Bisphenol A (BPA) exposure may increase the risk of asthma. Genetic polymorphisms of oxidative stress-related genes, glutathione S-transferases (GSTM1, GSTP1), manganese superoxide dismutase, catalase, myeloperoxidase, and microsomal epoxide hydrolase may be related to BPA exposure. The aim is to evaluate whether oxidative stress genes modulates associations of BPA exposure with asthma. METHODS: We conducted a case-control study comprised of 126 asthmatic children and 327 controls...
March 2018: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/29406986/was-ugo-foscolo-1778-1827-affected-by-alpha-1-antitrypsin-deficiency
#8
A Perciaccante, C Negri, A Coralli, P Charlier, O Appenzeller, R Bianucci
Niccolò Ugo Foscolo (1778-1827), known as Ugo, is one of the masters of the Italian poetry. A writer and a revolutionary, he embraced the ideals of the French Revolution and took part in the stormy political discussions, which the fall of the Republic of Venice had provoked. Despite his poor health, Foscolo lived an adventurous life serving as a volunteer in the Guardia Nazionale and in the Napoleonic army. Following Napoleon's fall (1814), he went into voluntary exile in early 1815. He reached London in Sept...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29404159/presence-of-headache-and-migraine-in-asthma-patients
#9
Muzaffer Onur Turan, Çiğdem Çelik Susuz, Pakize Ayşe Turan
OBJECTIVES: Migraine is a diseases characterized with severe headaches, with neurological and systemic findings. The purpose of this study is to investigate the prevalence of migraine and to examine whether there is a relationship between atopic disorders, parental history and migraine in asthma patients. MATERIAL AND METHODS: A total of 288 asthma outpatients, who had the diagnosis by an early or late test of reversibility showing a reversible airway obstruction according to hospital database were included...
April 2017: Turkish Thoracic Journal
https://www.readbyqxmd.com/read/29393212/toll-interacting-protein-tollip-inhibits-il-13-mediated-pulmonary-eosinophilic-inflammation-in-mice
#10
Yoko Ito, Niccolette Schaefer, Amelia Sanchez, David Francisco, Rafeul Alam, Richard J Martin, Julie G Ledford, Connor Stevenson, Di Jiang, Liwu Li, Monica Kraft, Hong Wei Chu
Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wild-type (WT) mice were inoculated intranasally with recombinant mouse IL-13 protein to examine lung inflammation...
January 27, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29392055/tnf-%C3%AE-and-il-1-%C3%AE-cytokine-gene-polymorphism-in-patients-with-nasal-polyposis
#11
Onur İsmi, Cengiz Özcan, Gürbüz Polat, Seval Kul, Kemal Görür, Tuğçe Pütürgeli
Objective: Nasal Polyp (NP) is a benign mass of the paranasal sinuses that protrudes into the nasal cavity. The exact underlying pathogenesis is not known. In this study we aimed to determine the genetic susceptibility of NP formation in relation to TNF-α-308 and IL-1β-511 promoter region gene polymorphisms. Methods: A total of 71 patients with NP with asthma (n=21) or without asthma (n=50) were taken as the study group, and 91 healthy volunteers were taken as the control group...
June 2017: Turkish Archives of Otorhinolaryngology
https://www.readbyqxmd.com/read/29389731/role-of-epigenetics-in-the-development-of-childhood-asthma
#12
Elizabeth J Davidson, Ivana V Yang
PURPOSE OF REVIEW: Epigenetic marks are emerging as mediators of genetics and the environment on complex disease phenotypes, including childhood asthma and allergy. RECENT FINDINGS: Epigenome-wide association studies over the past year have added to the growing body of evidence supporting significant associations of epigenetic regulation of gene expression and asthma and allergy. Studies in children have identified signatures of eosinophils in peripheral blood, Th2 cell transcription factors and cytokines in peripheral blood mononuclear cells, and epithelial dysfunction in the respiratory epithelium...
January 31, 2018: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29384926/glcci1-rs37973-a-potential-genetic-predictor-of-therapeutic-response-to-inhaled-corticosteroids-in-chinese-asthma-patients
#13
Yuzhu Xu, Hongxu Wu, Xiaojie Wu, Yongjian Xu, Jianping Zhao, Jungang Xie, Jun Yu
Glucocorticoids are the primary anti-inflammatory therapy for asthma, but their effects are characterized by some interindividual variability that might have a genetic basis.We aimed to determine the relationship between pulmonary function change and the variant of the glucocorticoid-induced transcript 1 (GLCCI1) gene in patients with asthma receiving long-term ICS treatment, the association of GLCCI1 genotypes and the level of GLCCI1 expression and cytokines production.A total of 418 patients with asthma, including 25 individuals from 11 families with a history of asthma, were enrolled...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29380695/how-to-control-asthma-with-personalized-management-where-do-we-stand-now
#14
Meng Wang, Yuan Yao, Shanqun Jiang, Fang Tao, Rui Tang, Jinlu Sun
Asthma is one of the most significant diseases worldwide and causes overwhelming costs physically and economically. The heterogeneity of asthma has been a hot topic, and an increasing amount of research has been conducted on this issue. The study of asthma has revealed various groups of asthma patients who share phenotypic characteristics that naturally elicit the need for personalized asthma therapy. Clinical evidence has shown that a 'one size fits all' approach does not apply to all asthma patients because of the large variability in treatment responses to asthma medication...
January 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29363184/functional-differences-in-airway-dendritic-cells-determine-susceptibility-to-ige-sensitisation
#15
Jonatan Leffler, Kyle T Mincham, Danny Mok, Fabian Blank, Patrick G Holt, Philip A Stumbles, Deborah H Strickland
Respiratory IgE-sensitisation to innocuous antigens increases the risk for developing diseases such as allergic asthma. Dendritic cells (DC) residing in the airways orchestrate the immune response following antigen exposure and their ability to sample and present antigens to naïve T cells in airway draining lymph nodes contributes to allergen-specific IgE-sensitisation. In order to characterise inhaled antigen capture and presentation by DC subtypes in vivo, we used an adjuvant-free respiratory sensitisation model using two genetically distinct rat strains, one of which is naturally resistant and the other naturally susceptible to allergic sensitisation...
December 30, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29361513/manipulation-of-dipeptidylpeptidase-10-in-mouse-and-human-in-vivo-and-in-vitro-models-indicates-a-protective-role-in-asthma
#16
Youming Zhang, Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Martin S Taylor, Lauren Chessum, Jackie Harrison, Loukia Tsaprouni, Ian M Adcock, Clare M Lloyd, William O Cookson, Miriam F Moffatt, Charlotte H Dean
We previously identified dipeptidyl-peptidase 10 (DPP10) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established (Dpp10145D )...
December 28, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29361392/preschool-wheeze-genes-and-treatment
#17
REVIEW
Chinedu Nwokoro, Jonathan Grigg
Preschool wheeze is a common but poorly understood cause of respiratory morbidity that is both distinct from and overlaps with infantile bronchiolitis and school age asthma. Attempts at classification by epidemiology, pathophysiology, therapeutic response and clinical phenotype are imperfect and yet fundamental to both treatment choice and research design. The four main therapeutic classes for preschool wheeze, namely beta2 agonists, anticholinergics, corticosteroids and leukotriene modifiers are employed with variable and often scanty evidence base, with evidence for a genetic influence on response variations...
December 5, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/29350142/lethal-respiratory-disease-associated-with-human-rhinovirus%C3%A2-c-in-wild-chimpanzees-uganda-2013
#18
Erik J Scully, Sarmi Basnet, Richard W Wrangham, Martin N Muller, Emily Otali, David Hyeroba, Kristine A Grindle, Tressa E Pappas, Melissa Emery Thompson, Zarin Machanda, Kelly E Watters, Ann C Palmenberg, James E Gern, Tony L Goldberg
We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R0) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y529 allele, which increases risk for rhinovirus C infection and asthma in human children...
February 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29344005/biological-clocks-their-relevance-to-immune-allergic-diseases
#19
REVIEW
Roberto Paganelli, Claudia Petrarca, Mario Di Gioacchino
The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm...
2018: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/29339772/foxo1-promotes-th9-cell-differentiation-and-airway-allergy
#20
Thomas S Buttrick, Wei Wang, Christina Yung, Kenneth G Trieu, Kruti Patel, Samia J Khoury, Xingbin Ai, Wassim Elyaman
T helper 9 (Th9) cells are effector CD4+ T cells that are characterized by the production of interleukin-9 (IL-9) and have been associated with allergic responses. Here, we found that the expression of the transcription factor forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic disruption of Foxo1 in CD4+ T cells caused a reduction in IL-9 expression while upregulating IL-17A and IFNγ production. Furthermore, chromatin immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation...
January 16, 2018: Scientific Reports
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