Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia
| Autor: | Luigi Laghi, Jens U. Marquardt, Lude Franke, Harm-Jan Westra, Ralf Kiesslich, Cisca Wijmenga, Julio Perez de la Serna, Rosario Cuomo, Jan Tack, Peter R. Galle, Ines Gockel, Henning G. Schulz, Giovanni Sarnelli, Daniel Drescher, Jessica Becker, Stefan Niebisch, Elisabeth Mangold, Anna Latiano, Paul I.W. de Bakker, V. Annese, Uberto Fumagalli, Antonio Ruiz de León, Michael T. Heneka, Alexander J. Eckardt, Per Hoffmann, Mira M. Wouters, Hans Dieter Allescher, Julian Zimmermann, Timo Hess, Werner Kneist, Elena Urcelay, Ana G. Vigo, Hauke Lang, Markus M. Nöthen, Gosia Trynka, Henning R. Gockel, Burkhard H.A. von Rahden, Vinod Kumar, Karl-Peter Hopfner, David Ramonet, Stefan Herms, Stefanie Heilmann, Michael Knapp, Michaela Müller, Guy E. Boeckxstaens, Johannes Schumacher, Manuel Mattheisen |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Ines, Gockel, Jessica, Becker, Mira M., Wouter, Stefan, Niebisch, Henning R., Gockel, Timo, He, David, Ramonet, Julian, Zimmermann, Ana Gonz?lez, Vigo, Gosia, Trynka, Antonio Ruiz de, Le?n, Julio P?rez de la, Serna, Elena, Urcelay, Vinod, Kumar, Lude, Franke, Harm Jan, Westra, Daniel, Drescher, Werner, Kneist, Jens U., Marquardt, Peter R., Galle, Manuel, Mattheisen, Vito, Annese, Anna, Latiano, Uberto, Fumagalli, Luigi, Laghi, Cuomo, Rosario, Sarnelli, Giovanni, Michaela, M?ller, Alexander J., Eckardt, Jan, Tack, Per, Hoffmann, Stefan, Herm, Elisabeth, Mangold, Stefanie, Heilmann, Ralf, Kiesslich, Burkhard H. A., von Rahden, Hans Dieter, Allescher, Henning G., Schulz, Cisca, Wijmenga, Michael T., Heneka, Hauke, Lang, Karl Peter, Hopfner, Markus M., N?then, Guy E., Boeckxstaen, Paul I. W., de Bakker, Michael, Knapp, Johannes, Schumacher |
| Rok vydání: | 2014 |
| Předmět: |
Male
Models Molecular Achalasia Immunogenetics Biology Major histocompatibility complex Polymorphism Single Nucleotide digestive system HLA-DQ alpha-Chains HLA-DQ Antigens HLA-DQ otorhinolaryngologic diseases Genetics medicine HLA-DQ beta-Chains Humans Genetic Predisposition to Disease Esophagus Alleles Genetic Association Studies Genetic association Motility disorder ASSOCIATION medicine.disease digestive system diseases Esophageal Achalasia INSIGHTS Logistic Models medicine.anatomical_structure Amino Acid Substitution Haplotypes Case-Control Studies Immunology biology.protein Female Idiopathic achalasia genetic MHC |
| Zdroj: | BASE-Bielefeld Academic Search Engine Nature Genetics, 46(8), 901-904. Nature Publishing Group Gockel, I, Becker, J, Wouters, M M, Niebisch, S, Gockel, H R, Hess, T, Ramonet, D, Zimmermann, J, Vigo, A G, Trynka, G, de León, A R, de la Serna, J P, Urcelay, E, Kumar, V, Franke, L, Westra, H-J, Drescher, D, Kneist, W, Marquardt, J U, Galle, P R, Mattheisen, M, Annese, V, Latiano, A, Fumagalli, U, Laghi, L, Cuomo, R, Sarnelli, G, Müller, M, Eckardt, A J, Tack, J, Hoffmann, P, Herms, S, Mangold, E, Heilmann, S, Kiesslich, R, von Rahden, B H A, Allescher, H-D, Schulz, H G, Wijmenga, C, Heneka, M T, Lang, H, Hopfner, K-P, Nöthen, M M, Boeckxstaens, G E, de Bakker, P I W, Knapp, M & Schumacher, J 2014, ' Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia ', Nature Genetics . https://doi.org/10.1038/ng.3029 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3029 |
| Popis: | Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus(1,2). This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ beta 1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 x 10(-19)). In addition, two amino acid substitutions in the. extracellular domain of HLA-DQ alpha 1 at position 41 (lysine encoded by HLA-DQA1*01:03; P = 5.60 x 10(-10)) and of HLA-DQ beta 1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P = 1.20 x 10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia. |
| Databáze: | OpenAIRE |
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