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, M.m., Niebisch, S., Gockel, H.r., Hess, T., Ramonet, D., Zimmermann, J., Vigo, A.g., Trynka, ., 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., et al.. - 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.
