HLA-DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of coeliac disease: A multicentre study

Int J Immunogenet. 2019 Apr;46(2):74-81. doi: 10.1111/iji.12415. Epub 2019 Feb 19.

Abstract

Background and purpose: Magnitude of gluten-specific T-cell responses in coeliac disease (CD) might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes.

Methods: We reviewed the charts of all coeliac patients attending to three Hungarian university clinics after 1997 and included those patients, who (a) were diagnosed with CD, (b) underwent high-resolution HLA typing and (c) were ≥18 years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate- and low-risk groups corresponded to a double, single and zero doses, respectively. We used ANOVA and Pearson's chi-squared test to explore association between HLA risk and clinical variables.

Results: A total of 727 coeliac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate and low HLA risk patients comprised 35.3%, 52.3% and 12.3% of the study population, respectively. Double dose of HLA-DQB1*02 was more frequent in patient with high tTGA level (>10 times the upper limit of normal; p = 0.045). Gene dose was not associated with younger age at diagnosis (p = 0.549), gender (p = 0.739), more severe diagnostic histology (p = 0.318), more frequent classical presentation (p = 0.846), anaemia (p = 0.611), metabolic bone disease (p = 0.374), dermatitis herpetiformis (p = 0.381) and autoimmune diseases (p = 0.837).

Conclusions: Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in CD.

Keywords: HLA-DQ2; Homozygosis; Phenotype; coeliac disease; gene dose.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Celiac Disease / diagnosis
  • Celiac Disease / enzymology*
  • Celiac Disease / genetics*
  • Child
  • Child, Preschool
  • Female
  • Gene Dosage
  • HLA-DQ Antigens / genetics*
  • Homozygote
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Neoplasms / pathology
  • Phenotype
  • Risk Assessment
  • Transglutaminases / metabolism*
  • Young Adult

Substances

  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • Transglutaminases