First genotype-phenotype study reveals HLA-DQβ1 insertion heterogeneity in high-resolution manometry achalasia subtypes

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\u2009=\u2009163), Germany (n\u2009=\u2009114), Greece (n\u2009=\u200970) 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\u2009=\u20090.038), 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.