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Asthma genetics

Winnie Schnass, Anke Hüls, Andrea Vierkötter, Ursula Krämer, Jean Krutmann, Tamara Schikowski
Childhood eczema results from an interplay of genetic and environmental factors including Traffic-Related Air Pollution (TRAP). In contrast, little is known about eczema in the elderly in general and its association with TRAP in particular. Animal experiments indicate that the arylhydrocarbon receptor (AHR) might link TRAP and eczema. We investigated (i) incidence and prevalence of eczema in elderly women, (ii) its association with long-term TRAP exposure and (iii) the effect modification by AHR polymorphism rs2066853...
June 13, 2018: International Journal of Hygiene and Environmental Health
Rachel S Kelly, Bo L Chawes, Kevin Blighe, Yamini V Virkud, Damien C Croteau-Chonka, Michael J McGeachie, Clary B Clish, Kevin Bullock, Juan C Celedón, Scott T Weiss, Jessica A Lasky-Su
BACKGROUND: Single-omic analyses have provided some insight into the basis of lung function in asthmatic children, but the underlying biological pathways are still poorly understood. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-regulated gene transcripts and metabolites in blood, among 325 children with asthma from the 'Genetic Epidemiology of Asthma in Costa Rica' study. The biology of modules associated with lung function; as measured by FEV1 , FEV1 /FVC-ratio, bronchodilator response, and airway responsiveness to methacholine, was explored...
June 13, 2018: Chest
Shanshan Jia, Pin Guo, Xiangjin Ge, Huanhuan Wu, Junhua Lu, Xiaofang Fan
Indoleamine 2, 3-dioxygenase (IDO) catalyzes the degradation of trytophan, which serves a key role in immune suppression via regulating the production of several metabolites. The present study aimed to explore the effects and mechanisms of IDO in the repair of human airway epithelium suppressed by dexamethasone (DEX). Cell viability, proliferation and migration were evaluated using a Cell Counting Kit-8 (CCK-8), 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling, and wound-healing assay, respectively...
July 2018: Experimental and Therapeutic Medicine
Se-Ra Lee, Won-Tae Kim, Tae Nam Kim, Jong Kil Nam, Woo Jin Kim, Sun-Hee Leem
In asthma and chronic obstructive pulmonary disease (COPD), mucins display disease-related alterations caused by airway mucus obstruction. MUC5AC, MUC5B and MUC8 are known as the major secretory mucins in human airway epithelial cells. Analysis of mucin genes has identified the presence of several features with a variable number of tandem repeats (VNTR; minisatellites) in the central region of each mucin. In our previous study, six minisatellites in the region of the MUC8 gene were identified, and the MUC8-MS5 minisatellite showed the highest heterozygosity among them...
January 2018: Genes & Genomics
A Bonaventure, L Orsi, J Rudant, S Goujon-Bellec, G Leverger, A Baruchel, Y Bertrand, B Nelken, M Pasquet, G Michel, N Sirvent, P Chastagner, S Ducassou, C Thomas, C Besse, D Hémon, J Clavel
BACKGROUND: Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions. METHODS: Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004...
June 5, 2018: Cancer Epidemiology
Sara Shagiwal, Herman T den Dekker, Johan C de Jongste, Guy G Brusselle, Vincent W V Jaddoe, Janine F Felix, Liesbeth Duijts
BACKGROUND: Genetic variants associated with adult lung function could already exert effects in childhood lung function. We aimed to examine the associations of adult lung function-related genetic variants with childhood lung function and asthma, and whether these associations were modified by atopic predisposition, tobacco smoke exposure, or early growth characteristics. METHODS: In a population-based prospective cohort study among 3,347 children, we selected 7 and 20 SNPs associated with adult forced expiratory volume in 1 second (FEV1 ) and FEV1 /forced vital capacity (FEV1 /FVC), respectively...
June 7, 2018: Pediatric Allergy and Immunology
Xiaochun Ma, Feng Long, Yan Yun, Jie Dang, Shijun Wei, Qian Zhang, Jinzhang Li, Haizhou Zhang, Wenlong Zhang, Zhengjun Wang, Qiji Liu, Chengwei Zou
A growing body of evidence has suggested the genetic association of ORMDL3 gene (ORMDL Sphingolipid Biosynthesis Regulator 3) polymorphisms with a diverse set of inflammatory disorders that include bronchial asthma, inflammatory bowel disease, ankylosing spondylitis and atherosclerosis. Gene functional investigations have revealed the particular relevance of ORMDL3 in endoplasmic reticulum stress, lipid metabolism and inflammatory reactions. Additionally, several reports have recently added a new dimension to our understanding of the modulation of ORMDL3 gene expression in inflammation...
June 2018: International Journal of Rheumatic Diseases
Amin Zakeri, Momtchilo Russo
Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genetic factors and exposure to environmental allergens, microbes, or microbial products where toll-like receptors (TLRs) play a pivotal role. TLRs recognize a wide range of microbial or endogenous molecules as well as airborne environmental allergens and act as adjuvants that influence positively or negatively allergic sensitization. TLRs are qualitatively and differentially expressed on hematopoietic and non-hematopoietic stromal or structural airway cells that when activated by TLRs agonists exert an immune-modulatory role in asthma development...
2018: Frontiers in Immunology
P Soares, K Fidler, J Felton, R Tavendale, A Hövels, S A Bremner, C N A Palmer, S Mukhopadhyay
BACKGROUND: Eczema and asthma are chronic diseases with onset usually before the age of 5 years. More than 50% of individuals with eczema will develop asthma and/or other allergic diseases. Several loss-of-function mutations in filaggrin (FLG) have been identified in patients with eczema. However, the association of FLG with healthcare use is unknown. OBJECTIVES: To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs...
May 31, 2018: British Journal of Dermatology
Jens Christian Richter, Kristina Jakobsson, Tahir Taj, Anna Oudin
Background: Atopic disorders are a global concern. Studies in migrant populations can illuminate the interplay of genetic and environmental factors. Exposures related to bad housing (indoor dampness, mould growth, crowding etc.) are likely to play a role in how socioeconomic inequalities can turn into health disparities for disadvantaged populations. The sizable immigrant population living in very poor-quality housing in Malmö, Sweden, became the focus of a cross-sectional study. Objective: To describe atopic disorders and sensitizations in a population living in substandard housing in Malmö, Sweden, with an emphasis on their relation to harmful exposures from the built environment...
2018: World Allergy Organization Journal
Zhaozhong Zhu, Phil H Lee, Mark D Chaffin, Wonil Chung, Po-Ru Loh, Quan Lu, David C Christiani, Liming Liang
Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg  = 0.75, P = 6.84 × 10-62 ). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci...
May 21, 2018: Nature Genetics
E J Ko, W I Heo, K Y Park, M-K Lee, S J Seo
Thymic stromal lymphopoietin(TSLP) is recognized as key cytokine in T helper type 2 (Th 2) cell differentiation and contributes to the pathogenesis of atopic disease. The TSLP gene on chromosome 5q22.1 and atopic cytokine gene on 5q31 are adjacent to each other. Based on their genetic location, it is suggested that the TSLP gene is involved in the progression or activity of atopic disease. Genetic association studies involving TSLP single nucleotide polymorphisms (SNPs) and allergic rhinitis or asthma in different racial group have yielded disparate and inconsistent results...
May 15, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Amin Khalifeh-Soltani, Deepti Gupta, Arnold Ha, Michael J Podolsky, Ritwik Datta, Kamran Atabai
Asthma affects ∼300 million people worldwide. Despite multiple treatment options, asthma treatment remains unsatisfactory in a subset of patients. Airway obstruction is a hallmark of allergic asthma and is largely due to airway smooth muscle hypercontractility induced by airway inflammation. Identification of molecular pathways that regulate airway smooth muscle hypercontractility is of considerable therapeutic interest. We previously identified roles for milk fat globule epidermal growth factor-like 8 (Mfge8) in opposing the effects of allergic inflammation on increasing airway smooth muscle contractile force...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
T H Zhu, T R Zhu, K A Tran, R K Sivamani, V Y Shi
Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces TH 2 inflammatory response and a thymic stromal lymphopoietin mediated pathway that further promotes barrier breakdown at distant sites including the intestinal and respiratory tract. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march...
May 15, 2018: British Journal of Dermatology
Y-L Yeh, M-W Su, B-L Chiang, Y-H Yang, C-H Tsai, Y L Lee
BACKGROUND: Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable in the clinic, especially for childhood asthma. OBJECTIVE: We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients. METHODS: Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays...
May 14, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Takehiko Yokomizo, Motonao Nakamura, Takao Shimizu
Leukotrienes, a class of arachidonic acid-derived bioactive molecules, are known as mediators of allergic and inflammatory reactions and considered to be important drug targets. Although an inhibitor of leukotriene biosynthesis and antagonists of the cysteinyl leukotriene receptor are clinically used for bronchial asthma and allergic rhinitis, these medications were developed before the molecular identification of leukotriene receptors. Numerous studies using cloned leukotriene receptors and genetically engineered mice have unveiled new pathophysiological roles for leukotrienes...
May 14, 2018: Journal of Clinical Investigation
Yue Huo, Hong-Yu Zhang
Asthma is a chronic disease that is caused by airway inflammation. The main features of asthma are airway hyperresponsiveness (AHR) and reversible airway obstruction. The disease is mainly managed using drug therapy. The current asthma drug treatments are divided into two categories, namely, anti-inflammatory drugs and bronchodilators. However, disease control in asthma patients is not very efficient because the pathogenesis of asthma is complicated, inducing factors that are varied, such as the differences between individual patients...
May 3, 2018: Genes
Todd D Terhune, Richard C Deth
There are similarities between the immune response following immunization with aluminum adjuvants and the immune response elicited by some helminthic parasites, including stimulation of immunoglobulin E (IgE) and eosinophilia. Immunization with aluminum adjuvants, as with helminth infection, induces a Th2 type cell mediated immune response, including eosinophilia, but does not induce an environment conducive to the induction of regulatory mechanisms. Helminths play a role in what is known as the hygiene hypothesis, which proposes that decreased exposure to microbes during a critical time in early life has resulted in the increased prevalence and morbidity of asthma and atopic disorders over the past few decades, especially in Western countries...
May 3, 2018: International Journal of Environmental Research and Public Health
Nadine Zwink, Ekkehart Jenetzky
BACKGROUND: Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically. METHODS: Studies published between 1977 and April 2017 were reviewed through systematic search in PubMed, ISI Web of Knowledge and Scopus databases. Furthermore, related and cross-referencing publications were reviewed...
May 10, 2018: Orphanet Journal of Rare Diseases
Aktriti Sinha, Anam Shariq, Khaled Said, Abhinav Sharma, D Jeffrey Newport, Ihsan M Salloum
PURPOSE OF REVIEW: Bipolar disorder (BD) medical comorbidity presents significant clinical and public health concerns with serious impact on health. The aim of this article is to present an updated narrative review of original research articles (case control, longitudinal cohort, and cross-sectional studies) and meta-analyses published in English language journals from January 2013 to May 2017 focusing on general medical comorbidity in BD, including the added risks of iatrogenic factors relevant to the treatment of BD...
May 7, 2018: Current Psychiatry Reports
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