Comprehensive epidemiological and genotype–phenotype analyses in a large European sample with idiopathic achalasia. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Becker, Jessica; Niebisch, Stefan; Ricchiuto, Arcangelo; Schaich, Eva J.; Lehmann, Gavin; Waltgenbach, Tobias; Schafft, Annette; Hess, Timo; Lenze, Frank; Venerito, Marino; Hüneburg, Robert; Lingohr, Philipp; Matthaei, Hanno; Seewald, Stefan; Scheuermann, Uwe; Kreuser, Nicole; Veits, Lothar; Wouters, Mira M.; Gockel, Henning R.; Lang, Hauke; Vieth, Michael; Müller, Michaela; Eckardt, Alexander J.; von Rahden, Burkhard H.A.; Knapp, Michael; Boeckxstaens, Guy E.; Fimmers, Rolf; Nöthen, Markus M.; Schulz, Henning G.; Gockel, Ines; Schumacher, Johannes;
• Is Part Of: European journal of gastroenterology & hepatology. Volume 28:Issue 6(2016:Jun.)
• Publication Date: 2016-06
• Subjects: allergic disorders -- autoimmune disorders -- epidemiological study -- genotype–phenotype analysis -- idiopathic achalasia -- virus infection; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Digestive organs -- Diseases; Liver -- Diseases; Periodicals; 616.33
• DOI: 10.1097/MEG.0000000000000602
• Languages: English
• ISSNs: 0954-691X

Abstract

Abstract : Background and aim: Although an eight-residue insertion in HLA-DQβ1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype–phenotype (G×P) analysis to gain further insights into the etiology of achalasia. Methods: We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls). For the G×P analysis, we stratified the patients into HLA-DQβ1 insertion carriers and noncarriers. Results: Our data show that patients are more often affected by viral infections before achalasia onset ( P <0.0001, most significantly for varicella zoster virus infections). In addition, allergic ( P =0.0005) and autoimmune disorders ( P =0.0007, most significantly for psoriasis and Sjögren's syndrome) represent comorbid disease conditions. First-degree relatives of patients also show higher prevalence rates of allergic disorders ( P =0.0007) and psoriasis ( P =0.016) compared with control relatives. Moreover, the G×P analysis reveals that achalasia is triggered by pregnancies in female HLA-DQβ1 insertion carriers ( P =0.031). Conclusion: Our data point to a role of viral infections in the development of achalasia. In addition, they provide evidence for a relationship between achalasia and allergic, as well as autoimmune, disorders. Furthermore, pregnancy seems to be a disease-triggering factor in female HLA-DQβ1 insertion carriers, which points to hormonal and/or immunosuppressive factors influencing disease development. Abstract : Supplemental Digital Content is available in the text.