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

Area of Science:

• Gastroenterology
• Genetics
• Immunology

Background:

• Achalasia is a primary esophageal motility disorder with an unknown etiology.
• A genetic risk variant, rs28688207 in HLA-DQB1, is associated with achalasia, suggesting immune-mediated pathogenesis.
• High-resolution manometry classifies achalasia into three subtypes.

Purpose of the Study:

• To conduct the first genotype-phenotype analysis of the rs28688207 variant.
• To investigate the frequency of the rs28688207 variant across high-resolution manometry achalasia subtypes.

Main Methods:

• A cross-sectional retrospective study involving 347 achalasia patients from multiple European centers.
• Genotyping for the rs28688207 insertion in all participants.
• Kruskal-Wallis test for genotype-phenotype analysis.

Main Results:

• The overall frequency of the rs28688207 insertion was 10.3%.
• Significant differences in the distribution of the rs28688207 insertion were observed across achalasia subtypes (p=0.038).
• The insertion was most prevalent in type I (14.6%), followed by type II (9.5%) and type III (6.3%).

Conclusions:

• The frequency of the HLA-DQB1 insertion varies among high-resolution manometry achalasia subtypes.
• The rs28688207 insertion is most prevalent in achalasia type I.
• This suggests a potentially greater role for immune-mediated mechanisms in type I achalasia pathogenesis.