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 × 109) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia
Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia / Gockel, I; Becker, J; Wouters, Mm; Niebisch, S; Gockel, Hr; Hess, T; Ramonet, D; Zimmermann, J; Vigo, Ag; Trynka, ; De León, Ar; De La Serna, Jp; Urcelay, E; Kumar, V; Franke, L; Westra, Hj; Drescher, D; Kneist, W; Marquardt, Ju; Galle, Pr; Mattheisen, M; Annese, V; Latiano, A; Fumagalli, U; Laghi, L; Cuomo, R; Sarnelli, G; Müller, M; Eckardt, Aj; Tack, J; Hoffmann, P; Herms, S; Mangold, E; Heilmann, S; Kiesslich, R; Von Rahden, Bha; Allescher, Hd; Schulz, Hg; Wijmenga, C; Heneka, Mt; Lang, H; Hopfner, Kp; Nöthen, ; Mm, ; Boeckxstaens, Ge; De Bakker, Piw; Knapp, M; Schumacher, J. - In: NATURE GENETICS. - ISSN 1061-4036. - 46:8(2014), pp. 901-904. [doi.org/10.1038/ng.3029]
Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia
Laghi L;
2014-01-01
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 × 109) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasiaI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
