First genotype-phenotype study reveals HLA-DQβ1 insertion heterogeneity in high-resolution manometry achalasia subtypes. Issue 1 (February 2019)

• Record Type: Journal Article
• Authors: Vackova, Zuzana; Niebisch, Stefan; Triantafyllou, Tania; Becker, Jessica; Hess, Timo; Kreuser, Nicole; Kanoni, Stavroula; Deloukas, Panos; Schüller, Vitalia; Heinrichs, Sophie KM; Thieme, René; Nöthen, Markus M; Knapp, Michael; Spicak, Julius; Gockel, Ines; Schumacher, Johannes; Theodorou, Dimitris; Martinek, Jan
• Is Part Of: United European Gastroenterology journal. Volume 7:Issue 1(2019)
• Page Start: 45
• Page End: 51
• Publication Date: 2019-02
• Subjects: Achalasia -- high-resolution manometry -- HLA-DQβ1 -- genetic risk variant; Gastroenterology -- Periodicals; Periodicals; 616.33005
• DOI: 10.1177/2050640618804717
• Languages: English
• ISSNs: 2050-6406

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.