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

• Published in: PloS one Vol. 10; no. 9; p. e0138324
• Main Authors: Tinto, Nadia, Cola, Arturo, Piscopo, Chiara, Capuano, Marina, Galatola, Martina, Greco, Luigi, Sacchetti, Lucia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2015; Public Library of Science (PLoS)
• Subjects: Adult; Age; Aged; Aged, 80 and over; Antigens; Autoimmune diseases; Biopsy; Biotechnology; Celiac disease; Celiac Disease - genetics; Disease; DQA1 protein; Drb1 protein; Enzyme-linked immunosorbent assay; Female; Gastroenterology; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease; Gluten; Haplotypes; Haplotypes - genetics; Health risks; Hepatology; Histocompatibility antigen HLA; HLA antigens; HLA-DQ Antigens - genetics; Humans; Identification methods; Immunofluorescence; Immunoglobulin A; Immunoglobulin G; Italy; Male; Medicine; Middle Aged; Oligonucleotides; Patients; Pediatrics; Physiological aspects; Retrospective Studies; Risk; Risk Factors; Small intestine; Young Adult; Italy; United States > US; Europe
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138324

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. 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. 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). 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.