HLA-DQ2/DQ8 and HLA-DQB1*02 homozygosity typing by real-time polymerase chain reaction for the assessment of celiac disease genetic risk: evaluation of a Spanish celiac population.

Celiac disease (CD) is a complex autoimmune disorder caused by ingestion of gluten in genetically susceptible individuals. Different genetic risk factors have been identified, but virtually all patients are human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive. We describe a new, fast, accurate and simple real-time polymerase chain reaction (PCR)-based assay for the genotyping and homozygosity analysis of the CD-related HLA alleles. The assay overcomes the major limitations of protocols currently in use, allowing HLA-DQ2/DQ8 genotyping by using only three real-time PCR reactions. For the appraisal of DQ2 homozygosity, only one more reaction is needed. These reactions are easily automated and suitable for large screening studies in diagnostic procedures, as it is demonstrated by their successful application in our HLA diagnostic laboratory. Finally, we assessed the clinical relevance of this real-time PCR-based assay by studying a cohort of fully characterized patients. As expected, all CD patients had at least one of the CD-associated alleles, and the highest CD risk was indicated by the presence of the HLA-DQ2.5 heterodimer (HLA-DQA1*05-DQB1*02) with HLA-DQB1*02 in homozygosity.

Ruiz-Ortiz E ，Montraveta M ，Cabré E ，Herrero-Mata MJ ，Pujol-Borrell R ，Palou E ，Faner R ... -  《-》

Influence of HLA-DQ2 and DQ8 on severity in celiac Disease.

Biagi F ，Bianchi PI ，Vattiato C ，Marchese A ，Trotta L ，Badulli C ，De Silvestri A ，Martinetti M ，Corazza GR ... -  《-》

Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles.

Pietzak MM ，Schofield TC ，McGinniss MJ ，Nakamura RM ... -  《-》

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in northwestern Mexico.

Type 1 diabetes (T1D) and celiac disease (CD) are the 2 most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has currently been an increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km(2)) in north-western Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. To compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient, and to identify the presence of celiac autoimmunity in the T1D group. The study included 397 Sonoran newborns, with 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora, and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. The Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8, with an HLA-DQ2:HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination showed a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases, and T1D and CD frequently appear together.

Mejía-León ME ，Ruiz-Dyck KM ，Calderón de la Barca AM 《-》

A multiplex assay to rapidly exclude HLA-DQ2.5 and HLA-DQ8 expression in patients at risk for celiac disease.

van Beek EM ，Roelandse-Koop EA ，Vijzelaar R ，Yilmaz R ，van Hoogstraten IM ，Schreurs MW ，Verheul AA ，van Houte AJ ，Kortlandt W ... -  《-》