Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease

Scand J Gastroenterol. 2004 Nov;39(11):1083-7. doi: 10.1080/00365520410007999.


Background: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed.

Methods: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR).

Results: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01).

Conclusions: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Celiac Disease / genetics*
  • Chromosomes, Human, Pair 14
  • Enhancer Elements, Genetic / genetics*
  • Female
  • Gene Frequency*
  • Genes, Immunoglobulin
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Locus Control Region / genetics
  • Male
  • Polymorphism, Genetic


  • Genetic Markers
  • Immunoglobulin Heavy Chains