Zuzana Vackova1, Stefan Niebisch2, Tania Triantafyllou3, Jessica Becker4,5, Timo Hess4,5, Nicole Kreuser2, Stavroula Kanoni6, Panos Deloukas6, Vitalia Schüller4,5, Sophie Km Heinrichs4,5, René Thieme2, Markus M Nöthen4,5, Michael Knapp7, Julius Spicak1, Ines Gockel2, Johannes Schumacher4,5, Dimitris Theodorou3, Jan Martinek1,8,9. 1. Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 2. Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany. 3. Foregut Surgery Department, Hippokration General Hospital of Athens, Athens, Greece. 4. Institute of Human Genetics, University of Bonn, Bonn, Germany. 5. Department of Genomics, University of Bonn, Bonn, Germany. 6. William Harvey Research Institute, University of London, London, UK. 7. Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Bonn, Germany. 8. Institute of Physiology, Charles University in Prague, Prague, Czech Republic. 9. Faculty of Medicine, Ostrava University, Ostrava, Czech Republic.
Abstract
Background: Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. Methods: This was a cross-sectional retrospective study. Achalasia patients from tertiary centres in the Czech Republic (n = 163), Germany (n = 114), Greece (n = 70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal-Wallis test was used for the genotype-phenotype analysis. Results: A total of 347 achalasia patients (type I - 89, II - 210, III - 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p = 0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). Conclusion: The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.
Background: Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. Methods: This was a cross-sectional retrospective study. Achalasiapatients from tertiary centres in the Czech Republic (n = 163), Germany (n = 114), Greece (n = 70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal-Wallis test was used for the genotype-phenotype analysis. Results: A total of 347 achalasiapatients (type I - 89, II - 210, III - 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p = 0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). Conclusion: The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.
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Authors: Jessica Becker; Stefan Niebisch; Arcangelo Ricchiuto; Eva J Schaich; Gavin Lehmann; Tobias Waltgenbach; Annette Schafft; Timo Hess; Frank Lenze; Marino Venerito; Robert Hüneburg; Philipp Lingohr; Hanno Matthaei; Stefan Seewald; Uwe Scheuermann; Nicole Kreuser; Lothar Veits; Mira M Wouters; Henning R Gockel; Hauke Lang; Michael Vieth; Michaela Müller; Alexander J Eckardt; Burkhard H A von Rahden; Michael Knapp; Guy E Boeckxstaens; Rolf Fimmers; Markus M Nöthen; Henning G Schulz; Ines Gockel; Johannes Schumacher Journal: Eur J Gastroenterol Hepatol Date: 2016-06 Impact factor: 2.566