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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
#1
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
#2
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-untreated-early-arthritis-implications-for-causal-gene-identification
#3
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. Seeking insight into genetic risk mechanisms, we conducted an expression quantitative trait locus (eQTL) analysis of confirmed genetic risk loci in CD4+ T cells and B cells from carefully phenotyped early arthritis patients naïve to therapeutic immunomodulation. METHODS: 344 patients donated RNA and DNA from purified B and/or CD4+ T-cells. Genotyping and global gene expression measurement were carried out using Illumina BeadChip microarrays...
November 28, 2017: 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
#4
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...
November 6, 2017: 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
#5
Hirotoshi Unno, Marina Miller, Peter Rosenthal, Andrew Beppu, Sudipta Das, David H Broide
No abstract text is available yet for this article.
September 27, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28889952/ormdl3-upregulates-airway-smooth-muscle-proliferation-contraction-and-ca-2-oscillations-in-asthma
#6
Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael Sanderson, David H Broide
BACKGROUND: Airway hyperresponsiveness (AHR) 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 ORMDL3, a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro, as well as influenced airway contractility and calcium flux in ASM in precision cut lung slices from WT and hORMDL3(Zp3-Cre) mice (which express increased levels of human ORMDL3)...
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
#7
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 hORMDL3(zp3-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 hORMDL3(zp3-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
#8
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
#9
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
#10
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
#11
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...
July 11, 2017: 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
#12
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
https://www.readbyqxmd.com/read/28534526/impact-of-genetic-polymorphisms-determining-leukocyte-neutrophil-count-on-chemotherapy-toxicity
#13
S J Glisovic, Y D Pastore, V Gagne, M Plesa, C Laverdière, J M Leclerc, D Sinnett, M Krajinovic
Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28461288/a-meta-analysis-of-genome-wide-association-studies-of-asthma-in-puerto%C3%A2-ricans
#14
Qi Yan, John Brehm, Maria Pino-Yanes, Erick Forno, Jerome Lin, Sam S Oh, Edna Acosta-Perez, Cathy C Laurie, Michelle M Cloutier, Benjamin A Raby, Adrienne M Stilp, Tamar Sofer, Donglei Hu, Scott Huntsman, Celeste S Eng, Matthew P Conomos, Deepa Rastogi, Kenneth Rice, Glorisa Canino, Wei Chen, R Graham Barr, Esteban G Burchard, Juan C Celedón
Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28427360/association-of-novel-polymorphisms-in-tmem39a-gene-with-systemic-lupus-erythematosus-in-a-chinese-han-population
#15
Xinze Cai, Wenyue Huang, Xudong Liu, Lining Wang, Yi Jiang
BACKGROUND: This study aimed to assess the association between 14 single nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3, GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han population sample. METHODS: We carried out a case-control study of 415 patients with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for genetic analysis was isolated from the blood of all subjects using standard phenol-chloroform method...
April 20, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28425483/a-genome-wide-association-study-identifies-six-novel-risk-loci-for-primary-biliary-cholangitis
#16
Fang Qiu, Ruqi Tang, Xianbo Zuo, Xingjuan Shi, Yiran Wei, Xiaodong Zheng, Yaping Dai, Yuhua Gong, Lan Wang, Ping Xu, Xiang Zhu, Jian Wu, Chongxu Han, Yueqiu Gao, Kui Zhang, Yuzhang Jiang, Jianbo Zhou, Youlin Shao, Zhigang Hu, Ye Tian, Haiyan Zhang, Na Dai, Lei Liu, Xudong Wu, Weifeng Zhao, Xiaomin Zhang, Zhidong Zang, Jinshan Nie, Weihao Sun, Yi Zhao, Yuan Mao, Po Jiang, Hualiang Ji, Qing Dong, Junming Li, Zhenzhong Li, Xinli Bai, Li Li, Maosong Lin, Ming Dong, Jinxin Li, Ping Zhu, Chan Wang, Yanqiu Zhang, Peng Jiang, Yujue Wang, Rohil Jawed, Jing Xu, Yu Zhang, Qixia Wang, Yue Yang, Fan Yang, Min Lian, Xiang Jiang, Xiao Xiao, Yanmei Li, Jingyuan Fang, Dekai Qiu, Zhen Zhu, Hong Qiu, Jianqiong Zhang, Wenyan Tian, Sufang Chen, Ling Jiang, Bing Ji, Ping Li, Guochang Chen, Tianxue Wu, Yan Sun, Jianjiang Yu, Huijun Tang, Michun He, Min Xia, Hao Pei, Lihua Huang, Zhuye Qing, Jianfang Wu, Qinghai Huang, Junhai Han, Wei Xie, Zhongsheng Sun, Jian Guo, Gengsheng He, M Eric Gershwin, Zhexiong Lian, Xiang Liu, Michael F Seldin, Xiangdong Liu, Weichang Chen, Xiong Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28358425/ormdl3-is-associated-with-airway-remodeling-in-asthma-via-the-erk-mmp-9-pathway
#17
Fei Yu, Yan Sun, Jiachen Yu, Zhen Ding, Jinrong Wang, Lanyun Zhang, Tiejing Zhang, Yun Bai, Yulin Wang
ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) has been previously implicated in asthma pathogenesis, its effect on airway remodeling remains to be elucidated. The present study examined the expression levels of ORMDL3 in a mouse model of asthma. Mice were divided into three groups: Asthmatic model (n=10), budesonide‑treated (n=10) and a control group (n=8). Asthma was induced by sensitization with ovalbumin (OVA) and aluminum hydroxide on day 1, 7 and 14. Subsequently mice were exposed to OVA three times per week from day 28...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28336364/mechanisms-and-roles-by-which-irf-3-mediates-the-regulation-of-ormdl3-transcription-in-respiratory-syncytial-virus-infection
#18
Xiao-Hua Wang, Jin Shu, Chun-Ming Jiang, Li-Li Zhuang, Wei-Xia Yang, Hui-Weng Zhang, Lu-Lu Wang, Lin Li, Xiao-Qing Chen, Rui Jin, Guo-Ping Zhou
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infancy, which is a major risk factor for recurrent wheezing and asthma. Orosomucoid 1-like protein 3 (ORMDL3) has been reported to associate with virus-triggered recurrent wheezing and asthma in children. However, little is known about how ORMDL3 is involved into RSV infection. In this study, we showed that the mRNA expression of ORMDL3 is significantly increased in the peripheral blood lymphocytes of infants with RSV-induced bronchiolitis compared with uninfected controls, also increased in bronchial epithelial cells and lung fibroblasts following RSV infection in vitro...
March 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28333149/upregulation-of-mir-665-promotes-apoptosis-and-colitis-in-inflammatory-bowel-disease-by-repressing-the-endoplasmic-reticulum-stress-components-xbp1-and-ormdl3
#19
Manying Li, Shenghong Zhang, Yun Qiu, Yao He, Baili Chen, Ren Mao, Yi Cui, Zhirong Zeng, Minhu Chen
MicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28275141/cutting-edge-targeting-epithelial-ormdl3-increases-rather-than-reduces-airway-responsiveness-and-is-associated-with-increased-sphingosine-1-phosphate
#20
Marina Miller, Arvin B Tam, James L Mueller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, Matthew D McGeough, Christine Vuong, Taylor A Doherty, Hal M Hoffman, Maho Niwa, David H Broide
In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium (Ormdl3(Δ2-3/Δ2-3)/CC10) to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen-challenged Ormdl3(Δ2-3/Δ2-3)/CC10 mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in Ormdl3(Δ2-3/Δ2-3)/CC10 and wild-type mice...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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