HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation

Murad, Hossam; Jazairi, Batoul; Khansaa, Issam; Olabi, Doaa; Khouri, Lina

doi:10.1186/s12876-018-0802-2

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…Our results shows that, in total 67.3% of Saudi CD patients were predicted to be the carriers of HLA CD-associated major risk alleles. We observed that Saudi individuals with homozygous HLA- DQ2.5 haplotype have a 4-fold higher risk to develop CD (OR = 4.074).This finding further confirms previous studies, which revealed a high risk associated with two copies of DQ2.5 among Europeans, Africans and Arabs ( Table 5 ) [ 17 , 22 , 24 , 27–31 ]. A recent study among Saudi children has reported that the homozygous DQ2.5 was seen in more CD cases than healthy controls.…”

Section: Discussionsupporting

confidence: 90%

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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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Section: Discussionsupporting

confidence: 90%

“…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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“…Previous small studies from India have reported absence of these two DQ antigens in 6–16% of patients with CeD 20–22 . Small studies in other populations indicate the absence of DQ2 and/or DQ8 in 12–35% of CeD patients 23–25 . Studies now indicate that other HLA‐DQ antigens, including DQ7 and DQ9, may confer risk to CeD 26,27 …”

Section: Discussionmentioning

confidence: 97%

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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“…After this publication, rare study has appeared, is the case of Almeida et al [2] and Murad et al [64], that given the existence of the estimated prevalence of these populations in other studies in the same region, were able to calculate the CD risk development in the populations of Brazil and Syria, respectively.…”

Section: Hla and The Importance Of Risk Genotypes In Laboratory Genotmentioning

confidence: 99%

“…Murad et al [64] found in the Syrian population, a slightly different risk for DQ2.5/DQ2.5, DQ2.5/DQ2.2, and DQ2.5/DQ8 genotypes and the associated risks were, respectively, 1:12.5, 1:20, and 1:10, emphasizing that in this population of origin other than Caucasians, the risk associated to these genotypes are somewhat different in terms of prevalence, but they continue to confer the greatest risks for developing CD (Figures 2 and 3). Because it is not possible to calculate the risk for the various world populations, there are many where the absence of disease prevalence data does not allow this calculation to be carried out, an estimate for populations of Caucasian origin seems to produce very close results suggesting that calculations are accurate in these populations.…”

Section: Hla and The Importance Of Risk Genotypes In Laboratory Genotmentioning

confidence: 99%

Genotype DQ2.5/DQ2.2 (ββ2/ββ2) and High Celiac Disease Risk Development

Nóbrega¹

2019

Celiac Disease - From the Bench to the Clinic

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Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. CD is considered one of the most wellcharacterized autoimmune diseases, having a described environmental factor, a well-established pathogenesis, associated genetic factors, and a well-established laboratory diagnosis, although it is still considered a difficult-to-classify disease. In the last decades, advances in laboratory diagnosis with the emergence of molecular biology techniques have allowed a specific characterization of the CD-associated genotypes and, although clinically the disease management was not modified by this factor, the follow-up of patients at risk of CD development has greatly benefited from the possibility of specifically finding the inherited genotype, and whether it represents a greater or lesser risk for developing the disease. In some populations, it is already possible to calculate the exact risk associated to the inherited genome by each individual, but the genotypes available in several countries sometimes disregard the relevance of searching beyond the genotypes DQ2.5/ DQ2.5, DQ2.5/DQ8, and DQ2.5/DQ2.2, which also present a high risk for developing the disease.

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HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation

Cited by 18 publications

References 33 publications

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

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

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

Genotype DQ2.5/DQ2.2 (ββ2/ββ2) and High Celiac Disease Risk Development

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