HLA‐DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland

Abstract

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world. We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7. This was done by clearly distinguishing DR7,DQ2 haplotypes from DR7,DQ9 haplotypes, and by "subtraction analysis" of haplotype frequencies. As reported in other populations, most of the patients without DR3 were heterozygous for DR7 and DR11 or 12 (DR5), or had DR4. We used PCR-RFLP and direct sequencing of amplified DNA to examine HLA-DR4 subtypes. The frequency of HLA-DR4 was markedly decreased in patients compared with controls (p = 0.000001) and there was a significant alteration of DR4 subtypes of the patients compared with controls (p = 0.0227). Moreover, all of the CD patients (5 of 5) with DR4 had a haplotype associated with the DQB1*0302 allele compared with only 11 of 23 control subjects with DR4. Our results in this population with exceptionally high risk of CD strongly support the DQ heterodimer hypothesis and suggest that the recently described sequence difference between the DQB1*02 alleles of DR3 and DR7 may contribute to a synergistic increased risk when these haplotypes are inherited together. In addition, our findings suggest a role for HLA-DQ in DR4-associated CD.

Study of HLA-DQB1 alleles in Spanish celiac patients and their first-degree relatives

“…These findings agree with other studies in European populations, e.g. Ireland, where Michalski et al [21] reported 71% of DQB1 02* positive CD cases. In our study, the DQB1 0201 frequency was slightly lower than in Finland, investigated by Polvi et al [28], where all the CD patients with both, silent and symptomatic forms, showed the DQB1 0201 allele.…”

“…Thirty celiac children, 13 boys (case number 1Ϫ13) and 17 girls (case number [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30], were studied in the Paediatrics and Microbiology (Immunology Laboratory) Departments of the Universitary Clinic Hospital "Lozano Blesa" in Zaragoza. All these patients were diagnosed according to the criteria established in 1990 by the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) [12].…”

Systematic review: the evidence base for long‐term management of coeliac disease

“…4,5 The remainder possess either HLA DQA1*05 or HLA DQB1*02, or express HLA DQ8 encoded by alleles DQA1*03 and DQB1*0302. 5,6 HLA DQ2 and DQ8 are within haplotypes that are also associated with other autoimmune conditions, such as type-1 diabetes mellitus, [7][8][9] autoimmune thyroid disease, [10][11][12] primary biliary cirrhosis, 13 Addison's disease, Sjogren's syndrome and autoimmune hepatitis, 14 although such an association has not always been found. 15,16 A genome wide association study identified non-HLA genes associated with CD.…”

Association between Celiac Disease and Chronic Hepatitis C Virus Infection

“…Furthermore, a solitary case report has shown that the cell-mediated inflammatory response to the HCV may involve T cells restricted to human leukocyte antigen (HLA)-DQ2, the class II HLA allele linked to celiac disease. 15 Hepatitis C virus is a blood-borne pathogen, which is the most common cause of posttransfusion hepatitis worldwide. Blood transfusion in many of patients with celiac disease for anemia might have led to HCV infection.…”