The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population

Line Lund Kårhus, Betina H Thuesen, Tea Skaaby, Jüri J Rumessen, Allan Linneberg, Line Lund Kårhus, Betina H Thuesen, Tea Skaaby, Jüri J Rumessen, Allan Linneberg

Abstract

Background: Human leukocyte antigen (HLA) DQ2 and DQ8 are important risk factors for some autoimmune diseases such as celiac disease (CD), but their possible role in other diseases and health conditions is not fully explored.

Objectives: The objective of this article is to examine the distribution of HLA DQ2 and HLA DQ8 in an adult general population, and their association with health indicators (diseases, symptoms and biomarkers).

Methods: In this cross-sectional, population-based study, 2293 individuals were screened for HLA DQ2 and DQ8; CD-associated alleles (DQA*0201*03*05/DQB*02*0301/0304*0302/0305) and DQB1*02 homozygosity were determined for screen-positive participants. The National Patient Registry provided diagnosis information.

Results: A total of 47.7% (1093/2293) individuals were positive for DQ2 and/or DQ8: 31.2% (716/2293) only DQ2, 11.9% (273/2293) only DQ8, 4.1% (93/2293) both DQ2 and DQ8. Among nine individuals diagnosed with CD, 89.9% (8/9) had DQ2.5cis, 22.2% (2/9) DQ8 and 22.2% (2/9) DQ2.2 (two both DQ2 and DQ8). HLA DQ2.5 was associated with higher thyroid-stimulating hormone levels, while DQ2/DQ8-positive participants had significantly lower prevalence of irritable bowel syndrome (IBS). DQ2/DQ8 were strongly associated with CD, but no other registry-based diagnoses.

Conclusion: In this general Danish population, 47.7% were HLA DQ2/DQ8 positive and thus potentially at risk for CD. All individuals with CD were DQ2/DQ8 positive; the majority DQ2.5. Surprisingly, DQ2/DQ8-positivity was associated with lower IBS prevalence.

Keywords: Celiac disease; HLA DQ2; HLA DQ8; epidemiology.

Figures

Figure 1.
Figure 1.
Overview of study and flow of participants in the cohort. *The participants were screened for HLA DQ8 and HLA DQ2 with the Celiac Gene Screen test, and the alleles associated with celiac disease were identified by the Celiac Gene Alleles test (BioDiagene, Palermo, Italy, distributed by Thermo Fisher Scientific, Allerød, Denmark). †Among the HLA DQ2 and HLA DQ8 positive individuals, 93 participants were both DQ2 and DQ8 positive. ‡Eleven participants positive for HLA DQ2 and/or HLA DQ8 were not allele classified. HLA: human leukocyte antigen.
Figure 2.
Figure 2.
Prevalence of celiac disease predisposition in a Danish general population. HLA: human leukocyte antigen.

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