Details

Autor(en) / Beteiligte

• Gockel, Ines
• Becker, Jessica
• Wouters, Mira M
• 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 E
• de Bakker, Paul I W
• Knapp, Michael
• Schumacher, Johannes

Titel

Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia

Ist Teil von

• Nature genetics, 2014-08, Vol.46 (8), p.901-904

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.