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Ormdl3

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https://www.readbyqxmd.com/read/28427360/association-of-novel-polymorphisms-in-tmem39a-gene-with-systemic-lupus-erythematosus-in-a-chinese-han-population
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28241063/role-of-dna-methylation-in-expression-control-of-the-ikzf3-gsdma-region-in-human-epithelial-cells
#7
Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, Samar Elzein, Raquel Farias, Julie Bérubé, Bianca Ho, Catherine Laprise, Cynthia G Goodyer, Simon Rousseau, Anna K Naumova
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7...
2017: PloS One
https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leucocytes
#8
Y-P Liu, V Rajamanikham, M Baron, S Patel, S K Mathur, E A Schwantes, C Ober, D J Jackson, J E Gern, R F Lemanske, J A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodelling and hyperresponsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN)-regulated chemokine CXCL10...
March 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28031110/-recombinant-platanus-pollen-allergen-2-rpla-a2-up-regulates-the-expression-of-ormdl3-mediated-by-gata3-in-nih3t3-cells
#9
Huiwen Zhang, Lili Zhuang, Rui Jin, Nannan Li, Guoping Zhou
Objective To identify the effect and mechanism of recombinant platanus pollen allergen 2 (rPla a2) on the transcription and expression of orosomucoid 1-like 3 (ORMDL3) gene in NIH3T3 cells. Methods Quantitative real-time PCR and Western blot analysis were used to detect the influence of rPla a2 on the mRNA and protein levels of ORMDL3 and GATA3. After transfection of GATA3 siRNA or pcDNA-GATA3, the role of GATA3 was evaluated in rPla a2 regulating ORMDL3 expression. Dual-luciferase reporter assay was performed to measure the influence of rPla a2 and GATA3 on ORMDL3 promoter activity...
January 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28030368/sphingolipids-ormdl3-and-asthma-what-is-the-evidence
#10
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...
March 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27932194/associations-between-nod2-irgm-and-ormdl3-polymorphisms-and-pediatric-onset-inflammatory-bowel-disease-in-the-lithuanian-population
#11
Gitana Pranculienė, Rūta Steponaitienė, Jurgita Skiecevičienė, Rūta Kučinskienė, Gediminas Kiudelis, Kęstutis Adamonis, Liutauras Labanauskas, Limas Kupčinskas
BACKGROUND AND OBJECTIVE: Recent GWAS and meta-analyses have revealed about 200 susceptibility genes/loci for inflammatory bowel diseases (IBD). However, only a small number of studies were performed in early-onset IBD. The aim of this study was to assess the association between NOD2, IL23R, ATG16L1, IRGM, IL10, NKX2-3 and ORMDL3 variants and early-onset IBD. MATERIALS AND METHODS: A total of 76 affected individuals (30 with Crohn's disease [CD] and 46 with ulcerative colitis [UC]) at the age of ≤17 years and 158 matched controls recruited in Lithuania were genotyped for the known genetic susceptibility variants in NOD2 (Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847)), IL23R (rs11209026), ATG16L1 (rs2241880), IRGM (rs4958847), IL10 (rs3024505), NKX2-3 (rs11190140) and ORMDL3 (rs2872507) genes...
2016: Medicina
https://www.readbyqxmd.com/read/27895690/rhinovirus-and-childhood-asthma-an-update
#12
REVIEW
Dae Jin Song
Asthma is recognized as a complex disease resulting from interactions between multiple genetic and environmental factors. Accumulating evidence suggests that respiratory viral infections in early life constitute a major environmental risk factor for the development of childhood asthma. Respiratory viral infections have also been recognized as the most common cause of asthma exacerbation. The advent of molecular diagnostics to detect respiratory viruses has provided new insights into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/27848966/17q21-asthma-risk-variants-switch-ctcf-binding-and-regulate-il-2-production-by-t-cells
#13
Benjamin Joachim Schmiedel, Grégory Seumois, Daniela Samaniego-Castruita, Justin Cayford, Veronique Schulten, Lukas Chavez, Ferhat Ay, Alessandro Sette, Bjoern Peters, Pandurangan Vijayanand
Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter the expression of ORMDL3; however, the molecular mechanisms by which these variants perturb gene expression and the cell types in which this effect is most prominent are unclear. We found several 17q21 variants overlapped enhancers present mainly in primary immune cell types. CD4(+) T cells showed the greatest increase (threefold) in ORMDL3 expression in individuals carrying the asthma-risk alleles, where ORMDL3 negatively regulated interleukin-2 production...
November 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27835674/lymphocyte-activation-dynamics-is-shaped-by-hereditary-components-at-chromosome-region-17q12-q21
#14
Amado Carreras-Sureda, Fanny Rubio-Moscardo, Alex Olvera, Jordi Argilaguet, Kerstin Kiefer, Beatriz Mothe, Andreas Meyerhans, Christian Brander, Rubén Vicente
Single nucleotide polymorphisms (SNPs) located in the chromosome region 17q12-q21 are risk factors for asthma. Particularly, there are cis-regulatory haplotypes within this region that regulate differentially the expression levels of ORMDL3, GSDMB and ZPBP2 genes. Remarkably, ORMDL3 has been shown to modulate lymphocyte activation parameters in a heterologous expression system. In this context, it has been shown that Th2 and Th17 cytokine production is affected by SNPs in this region. Therefore, we aim to assess the impact of hereditary components within region 17q12-q21 on the activation profile of human T lymphocytes, focusing on the haplotype formed by allelic variants of SNPs rs7216389 and rs12936231...
2016: PloS One
https://www.readbyqxmd.com/read/27826095/oroscomucoid-like-protein-3-ormdl3-transgenic-mice-have-reduced-levels-of-sphingolipids-including-sphingosine-1-phosphate-and-ceramide
#15
Marina Miller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, David H Broide
No abstract text is available yet for this article.
April 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27784618/benomyl-induced-effects-of-ormdl3-overexpression-via-oxidative-stress-in-human-bronchial-epithelial-cells
#16
Yoonjeong Jang, Ah Young Lee, Ji-Eun Kim, Sang-Hee Jeong, Jun Sung Kim, Myung-Haing Cho
The respiratory system is a major site of exposure route during pesticide use. Although pesticide exposure is associated with chronic respiratory diseases including asthma, the underlying pathophysiological mechanism remains to be elucidated. In this study, we investigated the in vitro effects of benomyl-induced ORMDL3 overexpression on the toxicological mechanism using the human bronchial epithelial cell line 16HBE14o-. Benomyl increased reactive oxygen species and Ca(2+) levels, and asthma-related ADAM33 and ORMDL3 expression in 16HBE14o- cells...
December 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27660012/gu-ben-fang-xiao-decoction-attenuates-sustained-airway-inflammation-by-suppressing-er-stress-response-in-a-murine-asthma-remission-model-of-respiratory-syncytial-virus-infection
#17
Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27658857/the-genetic-and-epigenetic-landscapes-of-the-epithelium-in-asthma
#18
Fatemeh Moheimani, Alan C-Y Hsu, Andrew T Reid, Teresa Williams, Anthony Kicic, Stephen M Stick, Philip M Hansbro, Peter A B Wark, Darryl A Knight
Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium...
2016: Respiratory Research
https://www.readbyqxmd.com/read/27645259/ormdl3-expression-levels-have-no-influence-on-the-activity-of-serine-palmitoyltransferase
#19
Assem Zhakupova, Nincy Debeuf, Michiel Krols, Wendy Toussaint, Leen Vanhoutte, Irina Alecu, Zoltán Kutalik, Peter Vollenweider, Daniela Ernst, Arnold von Eckardstein, Bart N Lambrecht, Sophie Janssens, Thorsten Hornemann
ORMDL proteins are believed to be negative regulators of serine palmitoyltransferase (SPT), which catalyzes the first and rate limiting step in sphingolipid (SL) de novo synthesis. Several single-nucleotide polymorphisms (SNPs) that are close to the ORMDL3 locus have been reported to increase ORMDL3 expression and to be associated with an elevated risk for early childhood asthma; however, the direct effect of ORMDL3 expression on SPT activity and its link to asthma remains elusive. In this study, we investigated whether ORMDL3 expression is associated with changes in SPT activity and total SL levels...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27623174/pulmonary-ormdl3-is-critical-for-induction-of-alternaria-induced-allergic-airways-disease
#20
Stephan Löser, Lisa G Gregory, Youming Zhang, Katrein Schaefer, Simone A Walker, James Buckley, Laura Denney, Charlotte H Dean, William O C Cookson, Miriam F Moffatt, Clare M Lloyd
BACKGROUND: Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. OBJECTIVE: We sought to investigate in vivo the functional role of ORMDL3 in disease inception. METHODS: An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined...
September 10, 2016: Journal of Allergy and Clinical Immunology
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