Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia

Eur J Gastroenterol Hepatol. 2016 Jun;28(6):689-95. doi: 10.1097/MEG.0000000000000602.


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.

MeSH terms

  • Adult
  • Alleles
  • Autoimmune Diseases / epidemiology*
  • Case-Control Studies
  • Chickenpox / epidemiology
  • Comorbidity
  • Esophageal Achalasia / epidemiology*
  • Esophageal Achalasia / genetics
  • Europe / epidemiology
  • European Continental Ancestry Group / genetics
  • Family
  • Female
  • Genotype
  • HLA-DQ beta-Chains / genetics*
  • Herpes Zoster / epidemiology
  • Herpesvirus 3, Human
  • Heterozygote
  • Humans
  • Hypersensitivity / epidemiology*
  • Male
  • Middle Aged
  • Phenotype
  • Pregnancy
  • Pregnancy Complications / epidemiology*
  • Pregnancy Complications / genetics
  • Psoriasis / epidemiology
  • Sjogren's Syndrome / epidemiology
  • Virus Diseases / epidemiology*


  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen