title: Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institutes for aHuman Genetics bMedical Biometry, Informatics, and Epidemiology Departments of cGenomics, Life & Brain Center dInternal Medicine I eGeneral, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn fDepartment of Medicine B, University Hospital Münster, Münster gDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg hDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig iDepartment of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz jDepartment of Gastroenterology, German Diagnostic Clinic, Wiesbaden kInstitute of Pathology, Klinikum Bayreuth, Bayreuth lDepartment of General, Visceral, Vascular and Pediatric Surgery, University of Würzburg, Würzburg mDepartment of General and Abdominal Surgery, Protestant Hospital Castrop-Rauxel, Castrop-Rauxel, Germany nTranslational Research Center for Gastrointestinal Disorders, Catholic University of Leuven, Leuven, Belgium oCenter of Gastroenterology, Klinik Hirslanden, Zürich, Switzerland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.forename: Stefan
authors.initials: S
authors.lastname: Niebisch
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Ricchiuto
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Schaich
authors.forename: Gavin
authors.initials: G
authors.lastname: Lehmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Waltgenbach
authors.forename: Annette
authors.initials: A
authors.lastname: Schafft
authors.forename: Timo
authors.initials: T
authors.lastname: Hess
authors.forename: Frank
authors.initials: F
authors.lastname: Lenze
authors.forename: Marino
authors.initials: M
authors.lastname: Venerito
authors.forename: Robert
authors.initials: R
authors.lastname: Hüneburg
authors.forename: Philipp
authors.initials: P
authors.lastname: Lingohr
authors.forename: Hanno
authors.initials: H
authors.lastname: Matthaei
authors.forename: Stefan
authors.initials: S
authors.lastname: Seewald
authors.forename: Uwe
authors.initials: U
authors.lastname: Scheuermann
authors.forename: Nicole
authors.initials: N
authors.lastname: Kreuser
authors.forename: Lothar
authors.initials: L
authors.lastname: Veits
authors.forename: Mira M
authors.initials: MM
authors.lastname: Wouters
authors.forename: Henning R
authors.initials: HR
authors.lastname: Gockel
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Eckardt
authors.forename: Burkhard H A
authors.initials: BH
authors.lastname: von Rahden
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Henning G
authors.initials: HG
authors.lastname: Schulz
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D000328:Adult; D000483:Alleles; D001327:Autoimmune Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D002644:Chickenpox / Q000453:epidemiology; D015897:Comorbidity; D004931:Esophageal Achalasia / Q000453:epidemiology* / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005190:Family; D005260:Female; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006562:Herpes Zoster / Q000453:epidemiology; D014645:Herpesvirus 3, Human; D006579:Heterozygote; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology* / Q000235:genetics; D011565:Psoriasis / Q000453:epidemiology; D012859:Sjogren's Syndrome / Q000453:epidemiology; D014777:Virus Diseases / Q000453:epidemiology*; D044465:White People / Q000235:genetics
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen