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High risk genotypes for celiac disease

F Clerget-Darpoux1, F Bouguerra, R Kastally

  • 1Unité de Recherches d'Epidémiologie Génétique, Institut National de la Santé et de la Recherche Médicale U155, Paris, France.

Comptes Rendus De L'Academie Des Sciences. Serie III, Sciences De La Vie
|October 1, 1994
PubMed
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Celiac disease risk is linked to HLA DQB1*0201 gene copies. Having two copies significantly increases celiac disease risk compared to other dimer carriers, a finding consistent across multiple populations.

Area of Science:

  • Immunogenetics
  • Gastroenterology

Background:

  • Celiac disease is strongly associated with specific Human Leukocyte Antigen (HLA) class II alleles.
  • The heterodimer DQA1*0501-DQB1*0201 is frequently found in celiac disease patients.

Purpose of the Study:

  • To investigate the specific contribution of the DQA1*0501-DQB1*0201 heterodimer to celiac disease risk.
  • To determine if the number of gene copies of DQB1*0201 influences celiac disease susceptibility.

Main Methods:

  • Analysis of HLA class II genotypes in a Tunisian population.
  • Replication of findings using published data from Italian, Czechoslovakian, United Kingdom, and Norwegian populations.

Main Results:

  • Celiac disease risk is independent of the number of possible heterodimers, cis/trans position of DQA1*0501 and DQB1*0201, and the number of DQA1*0501 copies.

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  • Risk is strongly dependent on the number of DQB1*0201 copies.
  • Individuals with a double dose of DQB1*0201 had a 6.8-fold increased risk of celiac disease in the Tunisian cohort.
  • This association was confirmed in independent European cohorts.

    • Conclusions:

    • The number of DQB1*0201 gene copies is a critical genetic factor influencing celiac disease risk.
    • This finding highlights the importance of DQB1*0201 dosage in the immunopathogenesis of celiac disease.