Background: Achalasia is a primary esophageal motility disorder that can be classified into three types (I-III) based on high-resolution manometry (HRM). Exact pathogenesis is unknown, but immune-mediated processes and genetic predisposition play a role, which is supported by finding of a genetic risk variant (rs28688207 insertion) in HLA-DQB1 gene that is strongly associated with achalasia. Per-oral endoscopic myotomy (POEM) has become a standard treatment for achalasia, but the long-term efficacy, safety and impact on esophageal physiology are not fully understood. The aims of our studies were to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 accross three HRM types of achalasia, to evaluate the efficacy and safety of POEM and to assess the post-POEM esophageal motility patterns. Patients and methods: These were three retrospective studies of prospectively collected data. Genotyping of the rs2868827 insertion was performed using real-time PCR in 347 patients from Czech Republic (n = 163), Germany (n = 114), Greece (n = 70). The efficacy and safety of POEM were evaluated in 133 patients treated in our center. The post-POEM esophageal motility was assessed using the Chicago Classification in 237 patients in whom HRM was performed prior to and after POEM....