Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia
Nature genetics. Bd. 46. H. 8. New York, NY: Nature America 2014 S. 901 - 904
Erscheinungsjahr: 2014
ISBN/ISSN: 1546-1718 ; 1061-4036
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
Doi/URN: 10.1038/ng.3029
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Inhaltszusammenfassung
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...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-DQbeta1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P=1.73x10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQalpha1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.60x10(-10)) and of HLA-DQbeta1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P=1.20x10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.» weiterlesen» einklappen
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Medizin
