High Frequency of Haplotype HLA-DQ7 in Celiac Disease Patients from South Italy: Retrospective Evaluation of 5,535 Subjects at Risk of Celiac Disease

PLoS One. 2015 Sep 23;10(9):e0138324. doi: 10.1371/journal.pone.0138324. eCollection 2015.

Abstract

Background: Celiac disease (CD) has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms) referred to our center during a 10-year period.

Methods: We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively.

Results: We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38%) than in DQ2/DQ8-positive CD patients (24%) (p<0.05).

Conclusion: Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Celiac Disease / genetics*
  • Female
  • Gene Frequency*
  • Genetic Predisposition to Disease*
  • HLA-DQ Antigens / genetics*
  • Haplotypes / genetics*
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • HLA-DQ Antigens
  • HLA-DQ7 antigen

Grants and funding

This work was supported by CEINGE Regione Campania (DGRC 1901/2009), MIUR PON 2007 -2013 project PON01_02589 and MIUR PON 2007–2013 project PON02_00619_3461281, POR Campania FSE 2007–2013, Project CRÈME. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.