HLA-DQ distribution and risk assessment of celiac disease in a Spanish center

Martínez-Ojinaga, Eva; Molina, Manuel; Polanco, Isabel; Urcelay, Elena; Núñez, Concepción

doi:10.17235/reed.2018.5399/2017

Cited by 19 publications

(12 citation statements)

References 25 publications

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“…Community‐based studies suggest that specific HLA‐DQB1 and ~DQA1 haplotypes confer approximately 5‐fold higher risk for CeD when compared to the absence of these haplotypes 14,16–19 . Among the healthy controls, the DQ2.5, DQ2.2, and DQ8.1 haplotypes were found in 11, 20, and 11%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

et al. 2021

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Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods HLA‐DQA1 and ~DQB1 loci were amplified, using long‐range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA‐international ImMunoGeneTics (IMGT) database. Results HLA‐DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64–12.47) and HLA‐DQB1*02:01 (OR 8.59, 95% CI 5.75–12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 8.56, 95% CI 5.67–13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 2.34, 95% CI 1.61–3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg.

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Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

et al. 2021

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“…The DQ2.2 haplotype is a low risk haplotype in CD patients in many countries [ 21 , 24 , 41 , 42 ]. In our study, predicted homozygous DQ2.2 was more frequent in control group (5.82%) than in cases (0.99%).…”

Section: Discussionmentioning

confidence: 99%

TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls

et al. 2021

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Background: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human Leukocyte Antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA)- DQ2 and/or DQ8 alleles. Therefore, this study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag Single Nucleotide Polymorphisms (SNP).Methods: HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using Real Time Polymerase Chain Reaction (RT-PCR) technique. Genotype calls were further validated by Sanger sequencing method.Results: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs.Conclusion: This study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared to the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

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“…In the context of disease association studies, it has been suggested that risk conferred by HLA can differ between distinct populations ( Ortiz-Fernández et al, 2014 ; Martínez-Ojinaga et al, 2018 ). A population-wise descriptive list of HLA alleles (at low resolution) as increased or decreased risk variants in disease phenotypes and disease progression in sarcoidosis has been outlined ( Kishore and Petrek, 2013 ; Fingerlin et al, 2015 ).…”

Section: Ngs Based Hla Typing In Population Studies and Its Applicatimentioning

confidence: 99%

“…Coeliac disease represents another example of a HLA associated disease with various European populations. This disease associates with HLA-DQA and - DQB genes and about 96% of European coeliac patients carry the HLA-DQ2.5 heterodimer ( DQA1 ∗ 05 - DQB1 ∗ 0201 ) ( Karell et al, 2003 ; Martínez-Ojinaga et al, 2018 ; Núñez et al, 2018 ) and in some reports differed among non-Europeans, for e.g., in Brazilians and Iranians, -DQ2.2 was not associated with coeliac disease ( Rostami-Nejad et al, 2014 ; Selleski et al, 2018 ). Also, the differential HLA basis of the GIMAP locus, which encoded proteins involved in the development of T and B lymphocytes, and Behçet’s disease was described in Asian and European populations ( Ortiz-Fernández et al, 2014 ).…”

Section: Ngs Based Hla Typing In Population Studies and Its Applicatimentioning

confidence: 99%

Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis

Kishore

Petřek

2018

Front. Genet.

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Unraveling of the HLA-related immunogenetic basis of several immune disorders is complex due to the extensive HLA polymorphism and strong linkage-disequilibrium between HLA loci. A lack of in phase sequence information, a relative deficiency of high resolution genotyping including non-coding regions and ambiguous haplotype assignment make it difficult to compare findings across association studies and to attribute a causal role to specific HLA alleles/haplotypes in disease susceptibility and modification of disease phenotypes. Earlier, historical antibody and DNA-based methods of HLA typing, primarily of low resolution at antigen/alellic group levels, yielded “indicative” findings which were partially improved by high-resolution DNA-based typing. Only recently, next-generation sequencing (NGS) approaches based on deep-sequencing of the complete HLA genes combined with bioinformatics tools began to provide the access to complete information at an allelic level. Analyzing HLA with NGS approaches, therefore, promises to provide further insight in the etiopathogenesis of several immune disorders in which HLA associations have been implicated. These range from coeliac disease and rheumatological conditions to even more complex disorders, such as type-1 diabetes, systemic lupus erythematosus and sarcoidosis. A systemic disease of unknown etiology, sarcoidosis has previously been associated with numerous HLA variants and also other gene polymorphisms, often in linkage with the HLA region. To date, the biological significance of these associations has only partially been defined. Therefore, more precise assignments of HLA alleles/haplotypes using NGS approaches could help to elucidate the exact role of HLA variation in the multifaceted etiopathogenesis of sarcoidosis, including epigenetic mechanisms. NGS-based HLA analyses may be also relevant for defining variable clinical phenotypes and for predicting the disease course or the response to current/plausible novel therapies.

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HLA-DQ distribution and risk assessment of celiac disease in a Spanish center

Cited by 19 publications

References 25 publications

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India

TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls

Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis

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