Title: Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia
Authors: Gockel, Ines ×
Becker, Jessica
Wouters, Mira
Niebisch, Stefan
Gockel, Henning R
Hess, Timo
Ramonet, David
Zimmermann, Julian
Vigo, Ana González
Trynka, Gosia
de León, Antonio Ruiz
de la Serna, Julio Pérez
Urcelay, Elena
Kumar, Vinod
Franke, Lude
Westra, Harm-Jan
Drescher, Daniel
Kneist, Werner
Marquardt, Jens U
Galle, Peter R
Mattheisen, Manuel
Annese, Vito
Latiano, Anna
Fumagalli, Uberto
Laghi, Luigi
Cuomo, Rosario
Sarnelli, Giovanni
Müller, Michaela
Eckardt, Alexander J
Tack, Jan
Hoffmann, Per
Herms, Stefan
Mangold, Elisabeth
Heilmann, Stefanie
Kiesslich, Ralf
von Rahden, Burkhard H A
Allescher, Hans-Dieter
Schulz, Henning G
Wijmenga, Cisca
Heneka, Michael T
Lang, Hauke
Hopfner, Karl-Peter
Nöthen, Markus M
Boeckxstaens, Guy
de Bakker, Paul I W
Knapp, Michael
Schumacher, Johannes #
Issue Date: Aug-2014
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:46 issue:8 pages:901-4
Article number: 10.1038/ng.3029
Abstract: Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. 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-DQβ1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 × 10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P = 5.60 × 10(-10)) and of HLA-DQβ1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P = 1.20 × 10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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