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

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; CDassociated 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. KeywordsCeliac disease, HLA DQ2, HLA DQ8, epidemiology Received: 29 December 2017; accepted: 21 February 2018 Key summary 1. Summarize the established knowledge on this subject:. Celiac disease is a lifelong autoimmune disease caused by a harmful immune response to gluten proteins in genetically susceptible individuals. . Human leukocyte antigen (HLA) DQ2 and HLA DQ8 are important risk factors for some autoimmune diseases such as celiac disease; however, their possible role in other diseases and health conditions is not fully explored. 2. What are the significant and/or new findings of this study? . Our study showed that 47.7% of individuals were HLA DQ2/DQ8 positive and thus potentially at risk for celiac disease in this general Danish population. . We found that all individuals with celiac disease were HLA DQ2/DQ8 positive; the majority DQ2.5. . Furthermore, HLA DQ2/DQ8 positivity was associated with lower prevalence of irritable bowel syndrome, but not with other diagnoses/diseases.

Frequency of HLA‐DQ, susceptibility genotypes for celiac disease, in Brazilian newborns

“…In conclusion, 43.7% of the analyzed individual tested positive for at least one of the CD predisposing HLA-DQ genotypes in our group of Brazilian NB. The highest frequency was found for DQ2.5 positive subjects (17.6%) followed by DQ8 (11.3%); DQ2.2 (10.3%); DQ8 and DQ2.2 (Karhus et al, 2018).…”

“…Our study was also comparable with a research performed in the Danish population, which analyzed the same genetic variants as assessed in our survey (Table ). However, they found a higher number of DQ2.5 positive samples (Karhus, Thuesen, Skaaby, Rumessen, & Linneberg, ).…”

Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series

“…Although there is some evidence that recipient HLA-DQA1*05:01 (DQ2 by serology) 18 and donor HLA-A3 antigen 19 may predispose to recurrent MN, these findings have not been confirmed. Importantly, although HLA-DQ2, HLA-DR17, and HLA-A3 antigens are common in the general population (20%-30%, 20,21 25%, 22 and 20%-25%, [23][24][25] respectively), a systematic evaluation of the association of recurrent MN with each of these antigens in donors and recipients has not been performed.…”

Distribution of HLA‐DQ risk genotypes for celiac disease in Ethiopian children

“…34 Our findings indicate that more than half (51.6%) of the Ethiopian population is carrying any of the DQ2.5, DQ2.2 and DQ8 haplotypes, which was comparable with the Swedish references (55.9%) and other previous studies performed on the general population in Australia (55.9%), 37 Iran (58%), 18 Saudi Arabia (52.7%), 25 but slightly higher than Brazil (43.7%) 38,39 and Denmark (47.7%). 40 Although this study is the largest HLAgenotyped Ethiopian population to date, it is limited by the fact that children included in the present study were enrolled from only one region and therefore may not represent the whole population in Ethiopia. We can therefore only speculate that our results might partly explain the low reported prevalence of the celiac disease in Ethiopia as compared with Sweden, 11 albeit the true prevalence in the general population is still unknown.…”