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https://www.readbyqxmd.com/read/29769657/correction-to-aryl-hydrocarbon-receptor-signaling-promotes-ormdl3-dependent-generation-of-sphingosine-1-phosphate-by-inhibiting-sphingosine-1-phosphate-lyase
#1
Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
In this article, published online 23 March 2018, the affiliation 10 of Zhou Y was incorrect. The affiliation should be "Children's Hospital and Institute of Biomedical Sciences, Fudan University. Key Laboratory of Neonatal Disease, Ministry of Health, 201102, Shanghai, China." The authors regret the errors.
May 16, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29753051/variation-in-doses-and-duration-of-particulate-matter-exposure-in-bronchial-epithelial-cells-results-in-upregulation-of-different-genes-associated-with-airway-disorders
#2
Priya Tripathi, Furong Deng, Anne M Scruggs, Yahong Chen, Steven K Huang
Exposure to particulate matter < 2.5 μm (PM2.5 ) is associated with a variety of airway diseases. Although studies have demonstrated that high doses of PM2.5 cause cytotoxicity and changes to gene expression in bronchial epithelial cells, the effect of lower doses and repeated exposure to PM2.5 are less well studied. Here, we treated BEAS-2B cells with varying doses of PM2.5 for 1-7 days and examined the expression of a variety of genes implicated in airway disorders. At high doses, PM2.5 increased the expression of IL6, TNF, TSLP, CSF2, PTGS2, IL4R, and SPINK5...
May 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29733354/deep-resequencing-of-ulcerative-colitis-associated-genes-identifies-novel-variants-in-candidate-genes-in-the-korean-population
#3
Chang Mo Moon, Seung Won Kim, Jae Bum Ahn, Hyun Woo Ma, Xiumei Che, Tae Il Kim, Won Ho Kim, Jae Hee Cheon
Background: Genome-wide association studies and meta-analyses have revealed the genetic background of ulcerative colitis (UC) by identifying common variants. However, these variants do not fully explain the disease variance in UC. To identify novel variants, we performed deep resequencing of UC-associated genes in Korean UC patients and subsequently investigated the functional roles of identified susceptibility genes. Methods: We performed targeted deep resequencing of 108 genes in 24 Korean UC patients and then performed association analysis with data from 126 healthy controls...
May 4, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29671030/abnormal-islet-sphingolipid-metabolism-in-type-1-diabetes
#4
Laurits J Holm, Lars Krogvold, Jane P Hasselby, Simranjeet Kaur, Laura A Claessens, Mark A Russell, Clayton E Mathews, Kristian F Hanssen, Noel G Morgan, Bobby P C Koeleman, Bart O Roep, Ivan C Gerling, Flemming Pociot, Knut Dahl-Jørgensen, Karsten Buschard
AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. METHODS: We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29588858/single-nucleotide-polymorphisms-in-asthma-candidate-genes-tbxa2r-adam33-fcer1b-and-ormdl3-in-pakistani-asthmatics-a-case-control-study
#5
Nusrat Saba, Osman Yusuf, Sadia Rehman, Saeeda Munir, Amna Noor, Muhammad Saqlain, Atika Mansoor, Ghazala Kaukab Raja
Background: Genetic variations in different loci and genes are important in asthma pathogenesis. There is much importance of various immunological pathways in the IgE secretion regulation. Alterations in any main part of these pathways can increase the risk of asthma development. Polymorphisms in these genetic markers can effect certain pathways which predict the asthma susceptibility. In the present study, SNPs directly or indirectly affecting the immunological process pathways are selected...
2018: Asthma Research and Practice
https://www.readbyqxmd.com/read/29572542/aryl-hydrocarbon-receptor-signaling-promotes-ormdl3-dependent-generation-of-sphingosine-1-phosphate-by-inhibiting-sphingosine-1-phosphate-lyase
#6
Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge...
March 23, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29374573/role-of-local-cpg-dna-methylation-in-mediating-the-17q21-asthma-susceptibility-gasdermin-b-gsdmb-ormdl-sphingolipid-biosynthesis-regulator-3-ormdl3-expression-quantitative-trait-locus
#7
Parul H Kothari, Weiliang Qiu, Damien C Croteau-Chonka, Fernando D Martinez, Andrew H Liu, Robert F Lemanske, Carole Ober, Jerry A Krishnan, Dan L Nicolae, Kathleen C Barnes, Stephanie J London, Albino Barraza-Villarreal, Steven R White, Edward T Naureckas, Joshua Millstein, W James Gauderman, Frank D Gilliland, Vincent J Carey, Scott T Weiss, Benjamin A Raby
No abstract text is available yet for this article.
January 31, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29348612/gwas-in-childhood-acute-lymphoblastic-leukemia-reveals-novel-genetic-associations-at-chromosomes-17q12-and-8q24-21
#8
Joseph L Wiemels, Kyle M Walsh, Adam J de Smith, Catherine Metayer, Semira Gonseth, Helen M Hansen, Stephen S Francis, Juhi Ojha, Ivan Smirnov, Lisa Barcellos, Xiaorong Xiao, Libby Morimoto, Roberta McKean-Cowdin, Rong Wang, Herbert Yu, Josephine Hoh, Andrew T DeWan, Xiaomei Ma
Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children's Oncology Group and the California Childhood Leukemia Study...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29296089/elevated-fractional-exhaled-nitric-oxide-and-blood-eosinophil-counts-are-associated-with-a-17q21-asthma-risk-allele-in-adult-subjects
#9
Elizabeth A Schwantes, Michael D Evans, Alex Cuskey, Alex Burford, Judith A Smith, Robert F Lemanske, Nizar N Jarjour, Sameer K Mathur
Background and objectives: Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) at the 17q21 locus conferring increased risk for childhood-onset asthma. Little is known about how these SNPs impact adult asthma patients. We sought to examine an adult population for associations between rs7216389 (17q21-associated SNP) and features of asthma including fractional exhaled nitric oxide (FeNO), eosinophil counts, and age of asthma onset. Methods: Subjects were genotyped at SNP rs7216389...
2018: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/29251255/effects-of-genetic-factors-to-inhaled-corticosteroid-response-in-children-with-asthma-a-literature-review
#10
Huong Duong-Thi-Ly, Ha Nguyen-Thi-Thu, Long Nguyen-Hoang, Hanh Nguyen-Thi-Bich, Timothy J Craig, Sy Duong-Quy
Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 ( TBX21) and Fc fragment of IgE receptor II ( FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 ( CRHR1), nuclear receptor subfamily 3 group C member 1 ( NR3C1), stress induced phosphoprotein 1 ( STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS...
December 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/29193869/cd4-and-b-lymphocyte-expression-quantitative-traits-at-rheumatoid-arthritis-risk-loci-in-patients-with-untreated-early-arthritis-implications-for-causal-gene-identification
#11
Nishanthi Thalayasingam, Nisha Nair, Andrew J Skelton, Jonathan Massey, Amy E Anderson, Alexander D Clark, Julie Diboll, Dennis W Lendrem, Louise N Reynard, Heather J Cordell, Stephen Eyre, John D Isaacs, Anne Barton, Arthur G Pratt
OBJECTIVE: Rheumatoid arthritis (RA) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus (eQTL) analysis of confirmed genetic risk loci in CD4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation. METHODS: RNA and DNA were isolated from purified B and/or CD4+ T cells obtained from the peripheral blood of 344 patients with early arthritis...
March 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29115563/ormdl3-may-participate-in-the-pathogenesis-of-bronchial-epithelial%C3%A2-mesenchymal-transition-in-asthmatic-mice-with-airway-remodeling
#12
Qi Cheng, Yunxiao Shang
Asthma is a common chronic respiratory disease in children that is caused by a complex interaction between genetic and environmental factors. Orosomucoid‑like 3 (ORMDL3) is a candidate gene that has been strongly associated with asthma; however, the underlying mechanisms are unknown. ORMDL3 regulates the expression of metalloproteinases and transforming growth factor‑β, and ORMDL3 transgenic mice exhibit increased airway remodeling. Therefore, ORMDL3 may be associated with airway remodeling. The present study attempted to examine the associations between ORMDL3 and the severity of airway remodeling in asthmatic mice, and also to determine whether ORMDL3 induces epithelial‑mesenchymal transition (EMT) in the bronchial epithelium...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28958904/activating-transcription-factor-6%C3%AE-atf6%C3%AE-regulates-airway-hyperreactivity-smooth-muscle-proliferation-and-contractility
#13
Hirotoshi Unno, Marina Miller, Peter Rosenthal, Andrew Beppu, Sudipta Das, David H Broide
No abstract text is available yet for this article.
January 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28889952/orosomucoid-like-3-ormdl3-upregulates-airway-smooth-muscle-proliferation-contraction-and-ca-2-oscillations-in-asthma
#14
Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael J Sanderson, David H Broide
BACKGROUND: Airway hyperresponsiveness is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. OBJECTIVE: We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3Zp3-Cre mice (which express increased levels of human ORMDL3 [hORMDL3])...
September 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28827284/rhinovirus-infection-of-ormdl3-transgenic-mice-is-associated-with-reduced-rhinovirus-viral-load-and-airway-inflammation
#15
Dae Jin Song, Marina Miller, Andrew Beppu, Peter Rosenthal, Sudipta Das, Maya Karta, Christine Vuong, Amit Kumar Mehta, Michael Croft, David H Broide
Orosomucoid like 3 (ORMDL3), a gene localized to chromosome 17q21, has been linked in epidemiologic studies to childhood asthma and rhinovirus (RV) infections. As the single nucleotide polymorphisms linking ORMDL3 to asthma are associated with increased expression of ORMDL3, we have used hORMDL3zp3-Cre mice (which have universal increased expression of human ORMDL3) to determine whether infection of these transgenic mice with RV influences levels of airway inflammation or RV viral load. RV infection of hORMDL3zp3-Cre mice resulted in reduced RV viral load assessed by quantitative real-time PCR (lung and airway epithelium), as well as reduced airway inflammation (total bronchoalveolar lavage cells, neutrophils, macrophages, and lymphocytes) compared with RV-infected wild-type mice...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28826527/chromosome-17q21-genes-ormdl3-and-gsdmb-in-asthma-and-immune-diseases
#16
REVIEW
Sudipta Das, Marina Miller, David H Broide
Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which regulates SERCA2b and IL-6, pathways of potential importance to asthma...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28747345/ormdl3-facilitates-the-survival-of-splenic-b-cells-via-an-atf6%C3%AE-endoplasmic-reticulum-stress-beclin1-autophagy-regulatory-pathway
#17
Jie Dang, Xianli Bian, Xiaochun Ma, Jiangxia Li, Feng Long, Shan Shan, Qianqian Yuan, Qian Xin, Yan Li, Fei Gao, Yaoqin Gong, Qiji Liu
The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice ( Ormdl3 -/- ), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28740106/environment-changes-genetic-effects-on-respiratory-conditions-and-allergic-phenotypes
#18
Yong Song, Michelle J Schwager, Vibeke Backer, Jing Guo, Celeste Porsbjerg, Siew-Kim Khoo, Ingrid A Laing, Eric K Moses, Peter LeSouëf, Guicheng Brad Zhang
The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28695611/prediction-of-type-1-diabetes-using-a-genetic-risk-model-in-the-diabetes-autoimmunity-study-in-the-young
#19
Brigitte I Frohnert, Michael Laimighofer, Jan Krumsiek, Fabian J Theis, Christiane Winkler, Jill M Norris, Anette-Gabriele Ziegler, Marian J Rewers, Andrea K Steck
BACKGROUND: Genetic predisposition for type 1 diabetes (T1D) is largely determined by human leukocyte antigen (HLA) genes; however, over 50 other genetic regions confer susceptibility. We evaluated a previously reported 10-factor weighted model derived from the Type 1 Diabetes Genetics Consortium to predict the development of diabetes in the Diabetes Autoimmunity Study in the Young (DAISY) prospective cohort. Performance of the model, derived from individuals with first-degree relatives (FDR) with T1D, was evaluated in DAISY general population (GP) participants as well as FDR subjects...
March 2018: Pediatric Diabetes
https://www.readbyqxmd.com/read/28588209/identification-of-the-functional-variant-driving-ormdl3-and-gsdmb-expression-in-human-chromosome-17q12-21-in-primary-biliary-cholangitis
#20
Yuki Hitomi, Kaname Kojima, Minae Kawashima, Yosuke Kawai, Nao Nishida, Yoshihiro Aiba, Michio Yasunami, Masao Nagasaki, Minoru Nakamura, Katsushi Tokunaga
Numerous genome-wide association studies (GWAS) have been performed to identify susceptibility genes to various human complex diseases. However, in many cases, neither a functional variant nor a disease susceptibility gene have been clarified. Here, we show an efficient approach for identification of a functional variant in a primary biliary cholangitis (PBC)-susceptible region, chromosome 17q12-21 (ORMDL3-GSDMB-ZPBP2-IKZF3). High-density association mapping was carried out based on SNP imputation analysis by using the whole-genome sequence data from a reference panel of 1,070 Japanese individuals (1KJPN), together with genotype data from our previous GWAS (PBC patients: n = 1,389; healthy controls: n = 1,508)...
June 6, 2017: Scientific Reports
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